YEAR-END REPORT - 2019 Published 23-Dec-2019 HPTS Issue Brief 12-23-19.37 Health Policy Tracking Service - Issue Briefs Pharmaceuticals and Medical Devices FDA Oversight Authored by Robert S. White, a Compliance Attorney on the publisher's editorial staff and a member of the Oklahoma bar. 12/23/2019 I. Drug Approvals FDA Approves New Treatment for Adult Patients with Rare, Life-Threatening Blood Disease On December 21, 2018, the FDA approved Ultomiris (ravulizumab) injection for the treatment of adult patients with paroxysmal [FN1] nocturnal hemoglobinuria (PNH), a rare and life-threatening blood disease. “The approval of Ultomiris will change the way that patients with PNH are treated,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “Prior to this approval, the only approved therapy for PNH required treatment every two weeks, which can be burdensome for patients and their families. Ultomiris uses a novel formulation so patients only need treatment every eight weeks, without compromising efficacy.” PNH is a rare acquired disorder that leads to the rupture or destruction of red blood cells (hemolysis). Patients with PNH are missing a certain protein that normally protects red blood cells from being destroyed by the patient's immune system. Patients with PNH have sudden, recurring episodes where red blood cells are prematurely destroyed which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, the following symptoms may occur: severe anemia, profound fatigue, shortness of breath, intermittent episodes of dark colored urine, kidney disease or recurrent pain. PNH can occur at any age, although it is most often diagnosed in young adulthood. The FDA granted this application Priority Review designation. Ultomiris also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Ultomiris to Alexion Pharmaceuticals. FDA Approves First Treatment for Rare Blood Disease On December 21, 2018, the FDA approved Elzonris (tagraxofusp-erzs) infusion for the treatment of blastic plasmacytoid dendritic cell [FN2] neoplasm (BPDCN) in adults and in pediatric patients, two years of age and older. “Prior to today's approval, there had been no FDA approved therapies for BPDCN. The standard of care has been intensive chemotherapy followed by bone marrow transplantation. Many patients with BPDCN are unable to tolerate this intensive therapy, so there is an urgent need for alternative treatment options,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. BPDCN is an aggressive and rare disease of the bone marrow and blood that can affect multiple organs, including the lymph nodes and the skin. It often presents as leukemia or evolves into acute leukemia. The disease is more common in men than women and in patients 60 years and older. The FDA granted this application Breakthrough Therapy and Priority Review designation. Elzonris also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Elzonris to Stemline Therapeutics. FDA Approves First Generic Version Of Sabril To Help Treat Seizures In Adults And Pediatric Patients With Epilepsy © 2020 Thomson Reuters. No claim to original U.S. Government Works. -1- On January 16, 2019, the FDA approved the first generic version of Sabril (vigabatrin) 500 mg tablets for treating complex partial seizures, also called focal seizures, as an adjunctive therapy (given with another primary treatment) in patients 10 years and older who [FN3] have responded inadequately to several alternative (refractory) treatments. “Prioritizing the approval of generic drugs to compete with medicines that face little or no competition is a key part of our efforts to support access and reduce drug costs to patients. The availability of high-quality generic alternatives of critically important medicines, once the period of patent protection or exclusivity has ended on the brand drug, helps advance access and saves consumers billions of dollars each year,” said FDA Commissioner Scott Gottlieb, M.D. “We know there has been past interest in developing a generic alternative to this product. Earlier this year, we also highlighted this drug, along with many others, on a list of off-patent, off-exclusivity branded drugs without approved generics, to clarify that there were no patents or exclusivities that should impede its approval. Today's action demonstrates that there is an open pathway to approving products like this one. We're especially focused on new policies aimed at making the generic review process more predictable, efficient and lower cost so we can entice more generic firms to enter this space, and help facilitate more generic drug launches after generic approvals. We know it's not enough just to approve a record number of generic medicines. We also want to see firms launch these products so that patients can benefit from their availability, and we intend to take steps to advance these goals.” Complex partial seizures, a common type of seizures, start in a specific area of the brain and can affect consciousness. Typically, complex partial seizures last between 30 and 90 seconds, and are often followed by a period of disorientation, confusion and/or fatigue. The FDA requires appropriate data and information to demonstrate that generic drugs meet the agency's rigorous approval standards to ensure quality drug products that are as safe and effective as their brand name counterparts. As with brand-name drugs, the FDA also inspects manufacturing and packaging facilities for generic drugs to ensure that they are capable of consistently producing quality products. The approval of generic vigabatrin tablets was granted to Teva Pharmaceuticals USA. FDA Approves First Therapy for the Treatment of Adult Patients with a Rare Blood Clotting Disorder On February 6, 2019, the FDA approved Cablivi (caplacizumab-yhdp) injection, the first therapy specifically indicated, in combination with plasma exchange and immunosuppressive therapy, for the treatment of adult patients with acquired thrombotic thrombocytopenic [FN4] purpura (aTTP), a rare and life-threatening disorder that causes blood clotting. “Patients with aTTP endure hours of treatment with daily plasma exchange, which requires being attached to a machine that takes blood out of the body and mixes it with donated plasma and then returns it to the body. Even after days or weeks of this treatment, as well as taking drugs that suppress the immune system, many patients will have a recurrence of aTTP,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “Cablivi is the first targeted treatment that inhibits the formation of blood clots. It provides a new treatment option for patients that may reduce recurrences.” Patients with aTTP develop extensive blood clots in the small blood vessels throughout the body. These clots can cut off oxygen and blood supply to the major organs and cause strokes and heart attacks that may lead to brain damage or death. Patients can develop aTTP because of conditions such as cancer, HIV, pregnancy, lupus or infections, or after having surgery, bone marrow transplantation or chemotherapy. Health care providers are advised to monitor patients closely for bleeding when administering Cablivi to patients who currently take anticoagulants. The FDA granted this application Priority Review designation. Cablivi also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Cablivi to Ablynx. FDA Panel Recommends Approval of Johnson & Johnson's Depression Drug On February 12, 2019, an advisory panel to the FDA recommended Johnson & Johnson's experimental nasal spray, which has a [FN5] compound similar to often-abused ketamine, for patients suffering from depression. The panel voted 14-2 in favor of the drug esketamine, developed to treat major depression in patients who have not benefited from at least two different therapies, saying its benefits outweighed the risks. One member in the panel abstained from voting on the question. Esketamine is a variation of the anesthetic ketamine, which is also abused as a recreational party drug with the street nickname Special K. FDA Approves New Nasal Spray Medication For Treatment-Resistant Depression On March 5, 2019, the FDA approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment- © 2020 Thomson Reuters. No claim to original U.S. Government Works. -2- resistant depression). Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a [FN6] Risk Evaluation and Mitigation Strategy (REMS). “There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life- threatening condition,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research. “Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA's drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safety concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient.” Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression. The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they received the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug's uses and risks. The patient self-administers Spravato nasal spray under the supervision of a health care provider in a certified doctor's office or clinic, and the spray cannot be taken home. The health care provider will instruct the patient on how to operate the nasal spray device. During and after each use of the nasal spray device, the health care provider will check the patient and determine when the patient is ready to leave. The FDA granted this application Fast Track and Breakthrough Therapy designations. The FDA granted the approval of Spravato to Janssen Pharmaceuticals, Inc. FDA Approves a New Generic Valsartan On March 12, 2019, the FDA approved a new generic of Diovan (valsartan). Valsartan is an angiotensin II receptor blocker (ARB) that treats high blood pressure and heart failure. The FDA prioritized the review of this drug application to help relieve the recent shortage of this critical medicine as a result of multiple recalls of generic valsartan products from several manufacturers due to the finding that [FN7] certain lots of valsartan and other ARB medicines contain nitrosamine impurities. “We know that the ongoing recalls to prevent certain lots of valsartan that contain unacceptable limits of impurities from reaching patients has resulted in a shortage of these important medicines,” said FDA Commissioner Scott Gottlieb, M.D. “So to address the public health consequences of these shortages, we've prioritized the review of generic applications for these valsartan products. When faced with a drug shortage situation, the FDA employs a number of strategies to help mitigate the effects of the shortage on patients. As part of that work, we look at where we may be able to prioritize review of pending generic applications of the medicine in shortage, or similar products. We hope that today's approval of this new generic will help reduce the valsartan shortage, and we remain committed to implementing measures to prevent the formation of these impurities during drug manufacturing processes for existing and future products. We'll continue to work with manufacturers so that more medicines like valsartan, that belong to a class of drugs called angiotensin II receptor blockers, can be approved that are free of nitrosamine impurities to continue to address this ongoing shortage.” Since last summer, the FDA has conducted a major investigation to address the presence of nitrosamine impurities in certain generic ARB products. The FDA has worked with companies to take swift action to remove any products with unacceptable impurities from the U.S. market, and continues evaluating other ARBs to ensure they are free of impurities. FDA scientists have made important strides in understanding how these impurities may form during the manufacturing process and the agency is working with international drug regulatory agencies to make new testing methods available. The FDA has also engaged drug manufacturers and helped facilitate manufacturing process changes to ensure ARBs are free of detectable levels of nitrosamine impurities. Now that this risk has been identified, the agency is implementing new requirements to guard against the development of these impurities in drugs. FDA Approves First Treatment For Post-Partum Depression On March 19, 2019, the FDA approved Zulresso (brexanolone) injection for intravenous (IV) use for the treatment of postpartum depression (PPD) in adult women. This is the first drug approved by the FDA specifically for PPD. “Postpartum depression is a serious condition that, when severe, can be life-threatening. Women may experience thoughts about harming themselves or harming their child. Postpartum depression can also interfere with the maternal-infant bond. This approval marks the first time a drug has been specifically approved to treat postpartum depression, providing an important new treatment option,” said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research. “Because of concerns about serious risks, including excessive sedation or sudden loss of consciousness during administration, Zulresso has been approved with a Risk Evaluation and Mitigation Strategy (REMS) and is only available to patients © 2020 Thomson Reuters. No claim to original U.S. Government Works. -3- through a restricted distribution program at certified health care facilities where the health care provider can carefully monitor the patient.” PPD is a major depressive episode that occurs following childbirth, although symptoms can start during pregnancy. As with other forms of depression, it is characterized by sadness and/or loss of interest in activities that one used to enjoy and a decreased ability to feel pleasure (anhedonia) and may present with symptoms such as cognitive impairment, feelings of worthlessness or guilt, or suicidal ideation. Zulresso will be available only through a restricted program called the Zulresso REMS Program that requires the drug be administered by a health care provider in a certified health care facility. The REMS requires that patients be enrolled in the program prior to administration of the drug. Zulresso is administered as a continuous IV infusion over a total of 60 hours (2.5 days). Because of the risk of serious harm due to the sudden loss of consciousness, patients must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring (monitors oxygen levels in the blood). While receiving the infusion, patients must be accompanied during interactions with their children. The FDA granted this application Priority Review and Breakthrough Therapy designation. Approval of Zulresso was granted to Sage Therapeutics, Inc. FDA Approves New Oral Drugs To Treat Multiple Sclerosis On March 26, 2019, the FDA approved Mayzent (siponimod) tablets to treat adults with relapsing forms of multiple sclerosis (MS), to [FN8] include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. On March 29, 2019, the FDA approved Mavenclad (cladribine) tablets to treat relapsing forms of multiple sclerosis (MS) in adults, to include relapsing-remitting disease and active secondary progressive disease. Mavenclad is not recommended for MS patients with clinically isolated syndrome. Because of its safety profile, the use of Mavenclad is generally recommended for patients who have had [FN9] an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. “Multiple sclerosis can have a profound impact on a person's life,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research. “We are committed to continuing to work with companies that are developing additional treatment options for patients with multiple sclerosis.” MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communications between the brain and other parts of the body. Most people experience their first symptoms of MS between the ages of 20 and 40. MS is among the most common causes of neurological disability in young adults and occurs more frequently in women than in men. For most people, MS starts with a relapsing-remitting course, in which episodes of worsening function (relapses) are followed by recovery periods (remissions). These remissions may not be complete and may leave patients with some degree of residual disability. Many, but not all, patients with MS experience some degree of persistent disability that gradually worsens over time. In some patients, disability may progress independent of relapses, a process termed secondary progressive multiple sclerosis (SPMS). In the first few years of this process, many patients continue to experience relapses, a phase of the disease described as active SPMS. Active SPMS is one of the relapsing forms of MS, and drugs approved for the treatment of relapsing forms of MS can be used to treat active SPMS. Later, many patients with SPMS stop experiencing new relapses, but disability continues to progress, a phase called non-active SPMS. The FDA granted approval of Mayzent to Novartis. The FDA granted approval of Mavenclad to EMD Serono, Inc. FDA Approves New Oral Testosterone Capsule For Treatment Of Men With Certain Forms Of Hypogonadism On March 27, 2019, the FDA approved Jatenzo (testosterone undecanoate), an oral testosterone capsule to treat men with certain forms of hypogonadism. These men have low testosterone levels due to specific medical conditions, such as genetic disorders like Klinefelter syndrome or tumors that have damaged the pituitary gland. Jatenzo should not be used to treat men with “age-related hypogonadism,” in which testosterone levels decline due to aging, even if these men have symptoms that appear to be related to low [FN10] testosterone. Jatenzo's benefits do not outweigh its risks for that use. “Jatenzo's oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who up until now have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, M.D, M.M.Sc., director of the Division of Bone, Reproductive and Urologic Products in the FDA's Center for Drug Evaluation and Research. “But it's important to emphasize that this drug should not, like other testosterone treatments, be used to treat older men with ‘age-related hypogonadism.’ The benefits of testosterone therapy, including Jatenzo, have not been established for this use, and Jatenzo's effects on raising blood pressure can increase the risks of heart attack, stroke and cardiovascular death in this population.” The FDA granted the approval of Jatenzo to Clarus Therapeutics. FDA Approves First Two-Drug Complete Regimen For HIV-Infected Patients Who Have Never Received Antiretroviral Treatment © 2020 Thomson Reuters. No claim to original U.S. Government Works. -4- On April 8, 3019, the FDA approved Dovato (dolutegravir and lamivudine), as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history and with no known or suspected substitutions associated with resistance to the individual components of Dovato. This is the first FDA-approved two-drug, fixed-dose, [FN11] complete regimen for HIV-infected adults who have never received treatment for HIV. “Currently, the standard of care for patients who have never been treated is a three-drug regimen. With this approval, patients who have never been treated have the option of taking a two-drug regimen in a single tablet while eliminating additional toxicity and potential drug interactions from a third drug,” said Debra Birnkrant, M.D., Director of the Division of Antiviral Products. “Having a drug-sparing treatment available that uses fewer drugs is beneficial to patients who may have issues taking multiple medications over a long period of time.” In Feb. 2019, the U.S. Department of Health and Humans Services announced a new initiative, Ending the HIV Epidemic: A Plan for [FN12] America , a once-in-a-generation opportunity to eliminate new HIV infections in our nation. This initiative will provide the hardest hit communities with the additional expertise, technology and resources required to address the HIV epidemic in their communities, focusing on certain geographic hotspots. The aim is to reduce new infections by 75 percent in the next five years and by 90 percent in the next ten years, averting more than 250,000 HIV infections in that span. The FDA granted approval of Dovato to ViiV Healthcare. FDA Approves New Treatment For Osteoporosis In Postmenopausal Women At High Risk Of Fracture On April 9, 2019, the FDA approved Evenity (romosozumab-aqqg) to treat osteoporosis in postmenopausal women at high risk of breaking a bone (fracture). These are women with a history of osteoporotic fracture or multiple risk factors for fracture, or those who [FN13] have failed or are intolerant to other osteoporosis therapies. More than 10 million people in the U.S. have osteoporosis, which is most common in women who have gone through menopause. People with osteoporosis have weakened bones that are more likely to fracture. “Today's approval provides women with postmenopausal osteoporosis who are at high risk of fracture with a new treatment that will reduce this risk,” said Hylton V. Joffe, M.D, M.M.Sc., director of the Center for Drug Evaluation and Research's Division of Bone, Reproductive and Urologic Products. “But Evenity may increase the risk of heart attack, stroke and cardiovascular death so it's important to carefully select patients for this therapy, which includes avoiding use in patients who have had a heart attack or stroke within the previous year.” Evenity is a monoclonal antibody that blocks the effects of the protein sclerostin and works mainly by increasing new bone formation. One dose of Evenity consists of two injections, one immediately following the other, given once a month by a health care professional. The bone forming effect of Evenity wanes after 12 doses so more than 12 doses should not be used. If osteoporosis therapy is needed after the 12 doses, patients should begin an osteoporosis treatment that reduces bone breakdown. The FDA granted the approval of Evenity to Amgen. FDA Approves First Targeted Therapy for Metastatic Bladder Cancer On April 12, 2019, the FDA granted accelerated approval to Balversa (erdafitinib), a treatment for adult patients with locally advanced or metastatic bladder cancer that has a type of susceptible genetic alteration known as FGFR3 or FGFR2, and that has progressed during or following prior platinum-containing chemotherapy. Patients should be selected for therapy with Balversa using an FDA-approved [FN14] companion diagnostic device. “We're in an era of more personalized or precision medicine, and the ability to target cancer treatment to a patient's specific genetic mutation or biomarker is becoming the standard, with advances being made in new disease types. Today's approval represents the first personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “FGFRs regulate important biological processes including cell growth and division during development and tissue repair. This drug works by targeting genetic alterations in FGFRs.” The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma. Bladder cancers are associated with genetic mutations that are present in the patient's bladder or entire urothelium (the lining of the lower urinary tract). Bladder cancer is the sixth most common cancer in the United States. Fibroblast growth factor (FGFR) alterations are present in approximately one in five patients with recurrent and refractory bladder cancer. The FDA granted the approval of Balversa to Janssen Pharmaceutical. FDA Approves First Generic Naloxone Nasal Spray to Treat Opioid Overdose On April 19, 2019, the FDA granted final approval of the first generic naloxone hydrochloride nasal spray, commonly known as Narcan, a life-saving medication that can stop or reverse the effects of an opioid overdose. The agency is also planning new steps to prioritize the review of additional generic drug applications for products intended to treat opioid overdose, along with the previously announced [FN15] action to help facilitate an over-the-counter naloxone product. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -5- “In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible. In addition to this approval of the first generic naloxone nasal spray, moving forward we will prioritize our review of generic drug applications for naloxone. The FDA has also taken the unprecedented step of helping to assist manufacturers to pursue approval of an over-the-counter naloxone product and is exploring other ways to increase the availability of naloxone products intended for use in the community, including whether naloxone should be co-prescribed with all or some opioid prescriptions to reduce the risk of overdose death,” said Douglas Throckmorton, M.D., deputy center director for regulatory programs in the FDA's Center for Drug Evaluation and Research. “All together, these efforts have the potential to put a vital tool for combatting opioid overdose in the hands of those who need it most – friends and families of opioid users, as well as first responders and community-based organizations. We're taking many steps to improve availability of naloxone products, and we're committed to working with other federal, state and local officials as well as health care providers, patients and communities across the country to combat the staggering human and economic toll created by opioid abuse and addiction.” This approval is the first generic naloxone nasal spray for use in a community setting by individuals without medical training; however, generic injectable naloxone products have been available for years for use in a health care setting. The FDA also has previously approved a brand-name naloxone nasal spray and an auto-injector for use by those without medical training. While business and other considerations may impact how quickly this product becomes available, this approval is an important step for the agency as it works toward expanding access to this live-saving drug. The FDA tentatively approved this generic drug product on June 8, 2018. Teva Pharmaceuticals USA Inc. has received final FDA approval to market generic naloxone nasal spray. FDA Approves First Treatment for Pediatric Patients with Lupus On April 26, 2019, the FDA approved Benlysta (belimumab) intravenous (IV) infusion for treatment of children with systemic lupus erythematosus (SLE) –often referred to as simply “lupus” – a serious chronic disease that causes inflammation and damage to various body tissues and organs. This is the first time that the FDA has approved a treatment for pediatric patients with SLE. Benlysta has been [FN16] approved for use in adult patients since 2011. “The agency expedited the review and approval of this application because Benlysta IV fulfils an unmet need for therapies, specifically in pediatric patients with SLE. While there is no cure for lupus, treatment can help our youngest patients control their disease with the hope of improving their quality of life and lowering their risk of long-term organ damage and disability,” said Janet Woodcock, M.D., director of the FDA's Center for Drug Evaluation and Research. While childhood-onset SLE is rare, when diagnosed, it is generally more active in children and adolescents than adult patients, particularly in how it impacts organs such as the kidneys and central nervous system. As a result of the disease starting early in life, pediatric patients with SLE are at a higher risk for developing increased organ damage and complications from the disease as well as adverse events from the life-long treatments usually required. The FDA granted this application a Priority Review designation. The FDA granted the approval of Benlysta to GlaxoSmithKline. FDA Approves First Treatment for All Genotypes of Hepatitis C in Pediatric Patients On April 30, 2019, the FDA approved Mavyret (glecaprevir and pibrentasvir) tablets to treat all six genotypes of hepatitis C virus (HCV) [FN17] in children ages 12 to 17. Mavyret was previously approved to treat HCV in adults in 2017. “Direct-acting antiviral drugs reduce the amount of HCV in the body by preventing the virus from multiplying, and in most cases, they cure HCV infection,” said Jeffrey Murray, M.D., M.P.H., deputy director of the Division of Antiviral Products in the FDA's Center for Drug Evaluation and Research. “Today's approval represents another treatment option for children and adolescents with HCV infection, but for the first time, in all genotypes of HCV.” HCV is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. According to the U.S. Centers for Disease Control and Prevention, an estimated 2.7 to 3.9 million people in the U.S. have chronic HCV, and children born to HCV-positive mothers are at risk for HCV infection. It is estimated that there are 23,000 to 46,000 children in the U.S. with HCV infection. The FDA granted the approval of Mavyret to AbbVie Inc. FDA Approves New Treatments for Heart Disease Caused by a Serious Rare Disease, Transthyretin Mediated Amyloidosis On May 3, 2019, the FDA approved Vyndaqel (tafamidis meglumine) and Vyndamax (tafamidis) capsules for the treatment of the heart disease (cardiomyopathy) caused by transthyretin mediated amyloidosis (ATTR-CM) in adults. These are the first FDA-approved treatments for ATTR-CM. Vyndaqel and Vyndamax have the same active moiety, tafamidis, but they are not substitutable on a milligram to milligram basis and their recommended doses differ. “Transthyretin-mediated amyloidosis is a rare, debilitating and often fatal disease,” said Norman Stockbridge, M.D., Ph.D., director of the Division of Cardiovascular and Renal Drugs in the FDA's Center for Drug Evaluation and Research. “The treatments we're approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis.” © 2020 Thomson Reuters. No claim to original U.S. Government Works. -6- ATTR is caused by the buildup of abnormal deposits of specific proteins known as amyloid in the body's organs and tissues, interfering with their normal functioning. These protein deposits most frequently occur in the heart and the peripheral nervous system. Heart involvement can result in shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms and death. Involvement of the peripheral nervous system can result in a loss of sensation, pain, or immobility in the arms, legs, hands and feet. Amyloid deposits can also affect the kidneys, eyes, gastrointestinal tract and central nervous system. The FDA granted Vyndaqel Fast Track, Priority Review and Breakthrough Therapy designations. Vyndaqel and Vyndamax each received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. Approval of Vyndaqel and Vyndamax were granted to FoldRx, a subsidiary of Pfizer. FDA Approves First Treatment for Children with Lambert-Eaton Myasthenic Syndrome On May 6, 2019, the FDA approved Ruzurgi (amifampridine) tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. The only other treatment approved for LEMS is only approved for use in adults. “We continue to be committed to facilitating the development and approval of treatments for rare diseases, particularly those in children,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research. “This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities.” LEMS is a rare autoimmune disorder that affects the connection between nerves and muscles and causes weakness and other symptoms in affected patients. In people with LEMS, the body's own immune system attacks the neuromuscular junction (the connection between nerves and muscles) and disrupts the ability of nerve cells to send signals to muscle cells. LEMS may be associated with other autoimmune diseases, but more commonly occurs in patients with cancer such as small cell lung cancer, where its onset precedes or coincides with the diagnosis of cancer. LEMS can occur at any age. The prevalence of LEMS specifically in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide. The FDA granted this application Priority Review and Fast Track designations. Ruzurgi also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Ruzurgi to Jacobus Pharmaceutical Company, Inc. FDA Approves First Anticoagulant (Blood Thinner) For Pediatric Patients To Treat Potentially Life-Threatening Blood Clots On May 16, 2019, the FDA approved Fragmin (dalteparin sodium) injection, for subcutaneous use, to reduce the recurrence of symptomatic venous thromboembolism (VTE) in pediatric patients one month of age and older. VTE can include deep vein thrombosis [FN18] (blood clot in the deep veins of the leg) and pulmonary embolism (blood clot in the lungs), which can lead to death. “Most children who have VTE are fighting a serious underlying primary illness such as cancer or congenital heart disease. Not only are they fighting a serious illness, having a condition like VTE can then lead to significant complications and even death,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “Prior to this approval, there had been no FDA-approved therapies to treat VTE in pediatric patients. Given the unmet need, we granted the Fragmin application priority review and today we are approving it as the first anticoagulant (blood thinner) indicated for pediatric patients. We remain committed to advancing treatments for children with unmet medical needs.” VTE usually develops as a secondary complication of underlying clinical conditions such as a venous catheter, cancer, infection, congenital heart disease, and trauma or surgery. Pediatric VTE is associated with an increased risk of in-hospital mortality, recurrent VTE and post-thrombotic syndrome (damage to vein). Fragmin was initially approved by the FDA in 1994 for adults and is a type of heparin, which works as an anticoagulant. The efficacy of Fragmin in children was based on a single trial with 38 pediatric patients with symptomatic deep vein thrombosis and/or pulmonary embolism. Patients were treated with Fragmin for up to three months, with starting doses by age and weight. At study completion, 21 patients achieved resolution of the qualifying VTE, seven patients showed regression, two patients showed no change, no patients experienced progression of the VTE and one patient experienced recurrence of VTE. The FDA granted this application Priority Review designation. Pfizer holds the application for Fragmin. FDA Approves Innovative Gene Therapy To Treat Pediatric Patients With Spinal Muscular Atrophy On May 24, 2019, the FDA approved Zolgensma (onasemnogene abeparvovec-xioi), the first gene therapy approved to treat children less than two years of age with spinal muscular atrophy (SMA), the most severe form of SMA and a leading genetic cause of infant [FN19] mortality. “Today's approval marks another milestone in the transformational power of gene and cell therapies to treat a wide range of diseases,” said Acting FDA Commissioner Ned Sharpless, M.D. “With each new approval, we see this exciting area of science continue to move beyond the concept phase into reality. The potential for gene therapy products to change the lives of those patients who may have © 2020 Thomson Reuters. No claim to original U.S. Government Works. -7- faced a terminal condition, or worse, death, provides hope for the future. The FDA will continue to support the progress in this field by helping to expedite the development of products for unmet medical needs through the use of review pathways designed to advance innovative, safe and effective treatment options.” SMA is a rare genetic disease caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the survival motor neuron (SMN) protein – a protein found throughout the body, which is critical for the maintenance and function of specialized nerve cells, called motor neurons. Motor neurons in the brain and spinal cord control muscle movement throughout the body. If there is not enough functional SMN protein, then the motor neurons die, leading to debilitating and often fatal muscle weakness. SMA caused by mutations in the SMN1 gene is generally classified into several subtypes, based on the age of onset and severity; infantile-onset SMA is the most severe and most common subtype. Children with this condition have problems holding their head up, swallowing and breathing. These symptoms may be present at birth or may present by the age of 6 months. “Children with SMA experience difficulty performing essential functions of life. Most children with this disease do not survive past early childhood due to respiratory failure” said Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research. “Patients with SMA now have another treatment option to minimize the progression of SMA and improve survival. This approval demonstrates the continued momentum of this promising new area of medicine and the FDA's commitment to supporting and helping expedite the development of these products.” The FDA granted this application Fast Track, Breakthrough Therapy, and Priority Review designations. Zolgensma also received Orphan Drug designation, which provides incentives to encourage the development of drugs for rare diseases. The FDA also awarded the manufacturer a rare pediatric disease priority review voucher, under a program intended to encourage the development of new drugs and biological products for the prevention and treatment of certain rare pediatric diseases. The FDA granted the approval of Zolgensma to AveXis Inc. FDA Approves First PI3K Inhibitor For Breast Cancer On May 24, 2019, the FDA approved Piqray (alpelisib) tablets, to be used in combination with the FDA-approved endocrine therapy fulvestrant, to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following progression [FN20] on or after an endocrine-based regimen. The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing. “Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient's specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “For this approval, we employed some of our newer regulatory tools to streamline reviews without compromising the quality of our assessment. This drug is the first novel drug approved under the Real- Time Oncology Review pilot program. We also used the updated Assessment Aid, a multidisciplinary review template that helps focus our written review on critical thinking and consistency and reduces time spent on administrative tasks.” Metastatic breast cancer is breast cancer that has spread beyond the breast to other organs in the body (most often the bones, lungs, liver or brain). When breast cancer is hormone-receptor positive, patients may be treated with anti-hormonal treatment (also called endocrine therapy), alone or in combination with other medicines, or chemotherapy. The FDA granted this application Priority Review designation. The FDA granted approval of Piqray to Novartis. The FDA granted approval of the therascreen PIK3CA RGQ PCR Kit to QIAGEN Manchester, Ltd. FDA Approves New Treatment For Hospital-Acquired And Ventilator-Associated Bacterial Pneumonia On June 3, 2019, the FDA approved a new indication for the previously FDA-approved drug, Zerbaxa (ceftolozane and tazobactam) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in patients 18 years and older. The FDA initially approved Zerbaxa in 2014 to treat complicated intra-abdominal infections and for complicated urinary [FN21] tract infections. “A key global challenge we face as a public health agency is addressing the threat of antimicrobial-resistant infections,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D. “Hospital-acquired and ventilator-associated bacterial pneumonia are serious infections that can result in death in some patients. New therapies to treat these infections are important to meet patient needs because of increasing antimicrobial resistance. That's why, among our other efforts to address antimicrobial resistance, we're focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections.” © 2020 Thomson Reuters. No claim to original U.S. Government Works. -8- HABP/VABP occur in patients in hospitals or other health care facilities and can be caused by a variety of bacteria. According to data from the U.S. Centers for Disease Control and Prevention, HABP and VABP are currently the second most common type of hospital- acquired infection in the United States, and are a significant issue in patients in the intensive care unit (ICU). The FDA granted the approval of Zerbaxa for the treatment of HABP/VABP to Merck & Co., Inc. FDA Approves First Treatment For Episodic Cluster Headache That Reduces The Frequency Of Attacks On June 4, 2019, the FDA approved Emgality (galcanezumab-gnlm) solution for injection for the treatment of episodic cluster headache in adults. “Emgality provides patients with the first FDA-approved drug that reduces the frequency of attacks of episodic cluster headache, an extremely painful and often debilitating condition,” said Eric Bastings, M.D., deputy director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research. “The FDA is committed to continuing to work with drug developers to bring treatments for unmet medical needs to patients.” Cluster headache is a form of headache that produces extreme pain and tends to occur in clusters, often at the same time(s) of the day, for several weeks to months. The headaches are accompanied by symptoms that may include: bloodshot eyes, excessive tearing of the eyes, drooping of the eyelids, runny nose and/or nasal congestion and facial sweating. Some people experience restlessness and agitation. Cluster headache attacks may strike several times a day, generally lasting between 15 minutes and three hours. Emgality is given by patient self-injection. It was first approved by the FDA in September 2018 for the preventive treatment of migraine in adults. The FDA granted the approval of Emgality to Eli Lilly. The FDA granted this application Priority Review and Breakthrough Therapy designation. FDA Approves New Treatment For Pediatric Patients With Type 2 Diabetes On June 17, 2019, the FDA approved Victoza (liraglutide) injection for treatment of pediatric patients 10 years or older with type 2 diabetes. Victoza is the first non-insulin drug approved to treat type 2 diabetes in pediatric patients since metformin was approved for pediatric use in 2000. Victoza has been approved to treat adult patients with type 2 diabetes since 2010. “The FDA encourages drugs to be made available to the widest number of patients possible when there is evidence of safety and efficacy,” said Lisa Yanoff, M.D, acting director of the Division of Metabolism and Endocrinology Products in the FDA's Center for Drug Evaluation and Research. “Victoza has now been shown to improve blood sugar control in pediatric patients with type 2 diabetes. The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with this disease.” Type 2 diabetes is the most common form of diabetes, occurring when the pancreas cannot make enough insulin to keep blood sugar at normal levels. Although type 2 diabetes primarily occurs in patients over the age of 45, the prevalence rate among younger patients has been rising dramatically over the past couple of decades. The Diabetes Report Card published by the U.S. Centers for Disease Control and Prevention estimates that more than 5,000 new cases of type 2 diabetes are diagnosed each year among U.S. youth younger than age 20. The FDA granted this application Priority Review. The approval of Victoza was granted to Novo Nordisk. FDA Expands Approval Of Treatment For Cystic Fibrosis To Include Patients Ages 6 And Older On June 21, 2019, the FDA expanded the indication for Symdeko (a combination of tezacaftor/ivacaftor) tablets for treatment of pediatric patients ages 6 years and older with cystic fibrosis who have certain genetic mutations. Last year, the FDA approved Symdeko to treat patients ages 12 and older who had the same specific genetic mutations. “Decades ago, patients with cystic fibrosis were generally expected to live until 10 years of age, with few surviving into their teenage years. Since then, wide-ranging research on the disease resulted in more treatments for this debilitating disease that have extended life expectancy and improved quality of life for patients, but there is still no cure,” said Banu Karimi-Shah, M.D., acting deputy director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA's Center for Drug Evaluation and Research. “Based on their individual genetic makeup, individuals may respond differently to certain drugs, so it is important to provide a variety of options. Today's approval of Symdeko for children as young as 6 years old provides an important treatment option for younger patients, and also provides more context on the safety and dosing specific to this population. The FDA remains committed to advancing novel treatment options for areas of unmet patient need, particularly in diseases impacting children.” Cystic fibrosis is a serious genetic disorder that results in the formation of thick mucus that builds up in the lungs, digestive tract and other parts of the body. It leads to severe respiratory and digestive problems as well as other complications such as infections and diabetes. Cystic fibrosis is caused by a defective protein that results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There are approximately 2,000 known mutations of the CFTR gene. Symdeko is used to treat patients who have two copies of the most common type of mutation – F508del mutation – or who have at least one of the mutations in the CFTR gene that is responsive to the active ingredients in Symdeko based on in vitro data and/or clinical evidence. Patients with cystic fibrosis and their caregivers should speak with a health care professional and have tests performed to understand which gene mutations patients have and whether Symdeko is likely to work for them. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -9- The FDA granted this application Priority Review. The approval of Symdeko was granted to Vertex Pharmaceuticals Incorporated. FDA Approves New Treatment For Hypoactive Sexual Desire Disorder In Premenopausal Women On June 21, 2019, the FDA approved Vyleesi (bremelanotide) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. “There are women who, for no known reason, have reduced sexual desire that causes marked distress, and who can benefit from safe and effective pharmacologic treatment. Today's approval provides women with another treatment option for this condition,” said Hylton V. Joffe, M.D., M.M.Sc., director of the Center for Drug Evaluation and Research's Division of Bone, Reproductive and Urologic Products. “As part of the FDA's commitment to protect and advance the health of women, we'll continue to support the development of safe and effective treatments for female sexual dysfunction.” HSDD is characterized by low sexual desire that causes marked distress or interpersonal difficulty and is not due to a co-existing medical or psychiatric condition, problems within the relationship or the effects of a medication or other drug substance. Acquired HSDD develops in a patient who previously experienced no problems with sexual desire. Generalized HSDD refers to HSDD that occurs regardless of the type of sexual activity, situation or partner. Vyleesi activates melanocortin receptors, but the mechanism by which it improves sexual desire and related distress is unknown. Patients inject Vyleesi under the skin of the abdomen or thigh at least 45 minutes before anticipated sexual activity and may decide the optimal time to use Vyleesi based on how they experience the duration of benefit and any side effects, such as nausea. Patients should not use more than one dose within 24 hours or more than eight doses per month. Patients should discontinue treatment after eight weeks if they do not report an improvement in sexual desire and associated distress. The FDA granted approval of Vyleesi to AMAG Pharmaceuticals. FDA Approves First Treatment For Chronic Rhinosinusitis With Nasal Polyps On June 26, 2019, the FDA approved Dupixent (dupilumab) to treat adults with nasal polyps (growths on the inner lining of the sinuses) accompanied by chronic rhinosinusitis (prolonged inflammation of the sinuses and nasal cavity). This is the first treatment approved for inadequately controlled chronic rhinosinusis with nasal polyps. “Nasal polyps can lead to loss of smell and often patients require surgery to remove the polyps,” said Sally Seymour, M.D., Director of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA's Center for Drug Evaluation and Research. “Dupixent provides an important treatment option for patients whose nasal polyps are not adequately controlled with intranasal steroids. It also reduces the need for nasal polyp surgery and oral steroids.” Dupixent is given by injection. The efficacy and safety of Dupixent were established in two studies with 724 patients, 18 years and older with chronic rhinosinusitis with nasal polyps who were symptomatic despite taking intranasal corticosteroids. Patients who received Dupixent had statistically significant reductions in their nasal polyp size and nasal congestion compared to the placebo group. Patients taking Dupixent also reported an increased ability to smell and required less nasal polyp surgery and oral steroids. The FDA granted this application Priority Review. The approval of Dupixent was granted to Regeneron Pharmaceuticals. FDA Approves First Treatment For Neuromyelitis Optica Spectrum Disorder, A Rare Autoimmune Disease Of The Central Nervous System On June 27, 2019, the FDA approved Soliris (eculizumab) injection for intravenous use for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. NMOSD is an autoimmune disease of the central nervous system that mainly affects the optic nerves and spinal cord. “Soliris provides the first FDA-approved treatment for neuromyelitis optica spectrum disorder, a debilitating disease that profoundly impacts patients' lives,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research. “This approval changes the landscape of therapy for patients with NMOSD. Having an approved therapy for this condition is the culmination of extensive work we have engaged in with drug companies to expedite the development and approval of safe and effective treatments for patients with NMOSD, and we remain committed to these efforts for other rare diseases.” In patients with NMOSD, the body's immune system mistakenly attacks healthy cells and proteins in the body, most often in the optic nerves and spinal cord. Individuals with NMOSD typically have attacks of optic neuritis, which causes eye pain and vision loss. Individuals also can have attacks resulting in transverse myelitis, which often causes numbness, weakness, or paralysis of the arms and legs, along with loss of bladder and bowel control. Most attacks occur in clusters, days to months to years apart, followed by partial recovery during periods of remission. Approximately 50% of patients with NMOSD have permanent visual impairment and paralysis caused by NMOSD attacks. According to the National Institutes of Health, women are more often affected by NMOSD than men and African Americans are at greater risk of the disease than Caucasians. Estimates vary, but NMOSD is thought to impact approximately 4,000 to 8,000 patients in the United States. NMOSD can be associated with antibodies that bind to a protein called aquaporin-4 (AQP4). Binding of the anti-AQP4 antibody appears to activate other components of the immune system, causing inflammation and damage to the central nervous system. The FDA granted the approval of Soliris to Alexion Pharmaceuticals. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -10- FDA Approves New Treatment For Refractory Multiple Myeloma On July 3, 2019, the FDA granted accelerated approval to Xpovio (selinexor) tablets in combination with the corticosteroid dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is resistant to several other forms of treatment, including at least two proteasome inhibitors, at least [FN22] two immunomodulatory agents, and an anti-CD38 monoclonal antibody. “While there is no cure for multiple myeloma, there are FDA-approved treatments to target the cancer and slow down the spread of the disease. Sadly, often over time, patients can exhaust all available treatments and still see their disease progress,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “Today we approved a treatment under our accelerated approval program that provides a treatment option for patients with multiple myeloma with no available therapy.” Multiple myeloma is cancer that begins in plasma cells (white blood cells that produce antibodies) and may also be referred to as plasma cell myeloma. Abnormal plasma cells build up in the bone marrow, forming tumors in many bones of the body. As more antibodies are made, it can cause blood to thicken and keep the bone marrow from making enough healthy blood cells. The exact causes of multiple myeloma are unknown, but it is more common in older people and African Americans. Xpovio in combination with dexamethasone was granted accelerated approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on an endpoint that is reasonably likely to predict a clinical benefit to patients. Further clinical trials are required to verify and describe Xpovio's clinical benefit. The FDA granted this application Fast Track designation. Xpovio also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Xpovio to Karyopharm Therapeutics. FDA Approves New Treatment For Complicated Urinary Tract And Complicated Intra-Abdominal Infections On July 17, 2019, the FDA approved Recarbrio (imipenem, cilastatin and relebactam), an antibacterial drug product to treat adults with [FN23] complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI). “The FDA remains focused on facilitating the development of safe and effective new antibacterial drugs to give patients more options to fight serious infections,” said Ed Cox, M.D., M.P.H., director for the Office of Antimicrobial Products in FDA's Center for Drug Evaluation and Research. “It is important that the use of Recarbrio be reserved for situations when there are limited or no alternative antibacterial drugs for treating a patient's infection.” Recarbrio is a three-drug combination injection containing imipenem-cilastatin, a previously FDA-approved antibiotic, and relebactam, a new beta-lactamase inhibitor. Recarbrio received FDA's Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act. As part of QIDP designation, Recarbrio was granted Priority Review under which the FDA's goal is to take action on an application within an expedited time frame. The FDA granted the approval of Recarbrio for the treatment to Merck & Co., Inc. FDA Approves First Generics Of Lyrica On July 19, 2019, the FDA approved multiple applications for first generics of Lyrica (pregabalin) for the management of neuropathic pain associated with diabetic peripheral neuropathy, for the management of postherpetic neuralgia, as an adjunctive therapy for the treatment of partial onset seizures in patients 17 years of age and older, for the management of fibromyalgia, and for the management [FN24] of neuropathic pain associated with spinal cord injury. “Today's approval of the first generics for pregabalin, a widely-used medication, is another example of the FDA's longstanding commitment to advance patient access to lower cost, high-quality generic medicines,” said Janet Woodcock, M.D., director of the FDA's Center for Drug Evaluation and Research. “The FDA requires that generic drugs meet rigorous scientific and quality standards. Efficiently bringing safe and effective generics to market so patients have more options to treat their conditions is a top priority for the FDA.” The FDA granted approvals for the generic versions of Lyrica to Alembic Pharmaceuticals, Alkem Laboratories, Amneal Pharmaceuticals, Dr. Reddy's Laboratories, InvaGen Pharmaceuticals, MSN Laboratories Ltd., Rising Pharmaceuticals, Inc., Sciegen Pharmaceuticals Inc., and Teva Pharmaceuticals. FDA Approves First Treatment For Severe Hypoglycemia That Can Be Administered Without An Injection On July 24, 2019, the FDA approved Baqsimi nasal powder, the first glucagon therapy approved for the emergency treatment of severe [FN25] hypoglycemia that can be administered without an injection. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -11- Severe hypoglycemia occurs when a patient's blood sugar levels fall to a level where he or she becomes confused or unconscious or suffers from other symptoms that require assistance from another person to treat. Typically, severe hypoglycemia occurs in people with diabetes who are using insulin treatment. Baqsimi is approved to treat severe hypoglycemia in patients with diabetes ages four and older. “People who are living with diabetes are at risk of their blood sugar levels falling below the normal range. There are many products on the market for those who need insulin, but until now, people suffering from a severe hypoglycemic episode had to be treated with a glucagon injection that first had to be mixed in a several-step process,” said Janet Woodcock, M.D., director of the FDA's Center for Drug Evaluation and Research. “This new way to administer glucagon may simplify the process, which can be critical during an episode, especially since the patient may have lost consciousness or may be having a seizure. In those situations, we want the process to treat the suffering person to be as simple as possible.” The FDA granted the approval of Baqsimi to Eli Lilly and Company. FDA Approves First Therapy For Rare Joint Tumor On August 2, 2019, the FDA approved Turalio (pexidartinib) capsules for the treatment of adult patients with symptomatic tenosynovial [FN26] giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not responsive to improvement with surgery. “TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient's quality of life and cause severe disability,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “Surgery is the primary treatment option, but some patients are not eligible for surgery, and tumors can recur, even after the procedure. Today's approval is the first FDA-approved therapy to treat this rare disease.” TGCT is a rare tumor that affects the synovium (thin layer of tissue that covers the surfaces of the joint spaces) and tendon sheaths (layer of membrane that covers tendons, which are fibrous tissue that connect muscle to bone). The tumor is rarely malignant but causes the synovium and tendon sheaths to thicken and overgrow, causing damage to surrounding tissue. The FDA granted this application Breakthrough Therapy designation and Priority Review designation. Turalio also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Turalio to Daiichi Sankyo. FDA Approves Oncology Drug that Targets a Key Genetic Driver of Cancer On August 15, 2019, the FDA granted accelerated approval to Rozlytrek (entrectinib), a treatment for adult and adolescent patients whose cancers have the specific genetic defect, NTRK (neurotrophic tyrosine receptor kinase) gene fusion and for whom there are no [FN27] effective treatments. “We are in an exciting era of innovation in cancer treatment as we continue to see development in tissue agnostic therapies, which have the potential to transform cancer treatment. We're seeing continued advances in the use of biomarkers to guide drug development and the more targeted delivery of medicine,” said FDA Acting Commissioner Ned Sharpless, M.D. “Using the FDA's expedited review pathways, including breakthrough therapy designation and accelerated approval process, we're supporting this innovation in precision oncology drug development and the evolution of more targeted and effective treatments for cancer patients. We remain committed to encouraging the advancement of more targeted innovations in oncology treatment and across disease types based on our growing understanding of the underlying biology of diseases.” This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than the location in the body where the tumor originated. The approval marks a new paradigm in the development of cancer drugs that are “tissue agnostic.” It follows the policies that the FDA developed in a guidance document released in 2018. The previous tissue agnostic indications approved by the FDA were pembrolizumab for tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in 2017 and larotrectinib for NTRK gene fusion tumors in 2018. “Today's approval includes an indication for pediatric patients, 12 years of age and older, who have NTRK-fusion-positive tumors by relying on efficacy information obtained primarily in adults. The FDA continues to encourage the inclusion of adolescents in clinical trials. Traditionally, clinical development of new cancer drugs in pediatric populations is not started until development is well underway in adults, and often not until after approval of an adult indication,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “Efficacy in adolescents was derived from adult data and safety was demonstrated in 30 pediatric patients.” Rozlytrek was granted accelerated approval. This approval commits the sponsor to provide additional data to the FDA. Rozlytrek also received Priority Review, Breakthrough Therapy and Orphan Drug designation. The approval of Rozlytrek was granted to Genentech, Inc. FDA Approves Treatment for Patients with Rare Bone Marrow Disorder [FN28] On August 16, 2019, the FDA approved Inrebic (fedratinib) capsules to treat adult patients with certain types of myelofibrosis. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -12- “Prior to today, there was one FDA-approved drug to treat patients with myelofibrosis, a rare bone marrow disorder. Our approval today provides another option for patients,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. “The FDA is committed to encouraging the development of treatments for patients with rare diseases and providing alternative options, as not all patients respond in the same way.” Myelofibrosis is a chronic disorder where scar tissue forms in the bone marrow and the production of the blood cells moves from the bone marrow to the spleen and liver, causing organ enlargement. It can cause extreme fatigue, shortness of breath, pain below the ribs, fever, night sweats, itching and bone pain. When myelofibrosis occurs on its own, it is called primary myelofibrosis. Secondary myelofibrosis occurs when there is excessive red blood cell production (polycythemia vera) or excessive platelet production (essential thrombocythemia) that evolves into myelofibrosis. The FDA granted this application Priority Review designation. Inrebic also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Inrebic to Impact Biomedicines, Inc., a wholly-owned subsidiary of Celgene Corporation. FDA Approves New Antibiotic To Treat Community-Acquired Bacterial Pneumonia [FN29] On August 19, 2019, the FDA approved Xenleta (lefamulin) to treat adults with community-acquired bacterial pneumonia. “This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease,” said Ed Cox, M.D., M.P.H., director of FDA's Office of Antimicrobial Products. “For managing this serious disease, it is important for physicians and patients to have treatment options. This approval reinforces our ongoing commitment to address treatment of infectious diseases by facilitating the development of new antibiotics.” Community-acquired pneumonia occurs when someone develops pneumonia in the community (not in a hospital). Pneumonia is a type of lung infection that can range in severity from mild to severe illness and can affect people of all ages. According to data from the Centers from Disease Control and Prevention, each year in the United States, about one million people are hospitalized with community-acquired pneumonia and 50,000 people die from the disease. Xenleta received FDA's Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act. As part of QIDP designation, Xenleta was granted Priority Review under which the FDA's goal is to take action on an application within an expedited time frame. The FDA granted the approval of Xenleta to Nabriva Therapeutics. FDA Approves First Treatment For Patients With Rare Type Of Lung Disease On September 6, 2019, the FDA approved Ofev (nintedanib) capsules to slow the rate of decline in pulmonary function in adults with interstitial lung disease associated with systemic sclerosis or scleroderma, called SSc-ILD. It is the first FDA-approved treatment for this [FN30] rare lung condition. “Patients suffering from scleroderma need effective therapies, and the FDA supports the efforts of drug companies that are designing and conducting the clinical trials necessary to bring treatment options to scleroderma patients,” said Nikolay Nikolov, M.D., associate director for Rheumatology of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA's Center for Drug Evaluation and Research. “Nintedanib is now a treatment option to slow the rate of decline in pulmonary function in patients who have interstitial lung disease from scleroderma.” Scleroderma is a rare disease that causes tissue throughout the body, including the lungs and other organs, to thicken and scar. Interstitial lung disease or ILD is a condition affecting the interstitium, which is part of the lung's structure, and is one of the most common disease manifestations of sclerderma. SSc-ILD is a progressive lung disease in which lung function declines over time, and it can be debilitating and life-threatening. ILD is the leading cause of death among people with scleroderma, typically resulting from a loss of pulmonary function that occurs when the lungs cannot supply enough oxygen to the heart. Approximately 100,000 individuals in the United States have scleroderma, and approximately half of scleroderma patients have SSc-ILD. The FDA granted the approval of Ofev to treat SSc-ILD to Boehringer Ingelheim Pharmaceuticals Inc. FDA Approves First Oral GLP-1 Treatment For Type 2 Diabetes On September 20, 2019, the FDA approved Rybelsus (semaglutide) oral tablets to improve control of blood sugar in adult patients with type 2 diabetes, along with diet and exercise. Rybelsus is the first glucagon-like peptide (GLP-1) receptor protein treatment approved for use in the United States that does not need to be injected. GLP-1 drugs are non-insulin treatments for people with type 2 diabetes. [FN31] “Patients want effective treatment options for diabetes that are as minimally intrusive on their lives as possible, and the FDA welcomes the advancement of new therapeutic options that can make it easier for patients to control their condition,” said Lisa Yanoff, M.D, acting director of the Division of Metabolism and Endocrinology Products in the FDA's Center for Drug Evaluation and Research. “Before this © 2020 Thomson Reuters. No claim to original U.S. Government Works. -13- approval, patients did not have an oral GLP1 option to treat their type 2 diabetes, and now patients will have a new option for treating type 2 diabetes without injections.” Type 2 diabetes is the most common form of diabetes, occurring when the pancreas cannot make enough insulin to keep blood sugar at normal levels. GLP-1, which is a normal body hormone, is often found in insufficient levels in type 2 diabetes patients. Like GLP-1, Rybelsus slows digestion, prevents the liver from making too much sugar, and helps the pancreas produce more insulin when needed. The approval of Rybelsus was granted to Novo Nordisk. FDA Approves First Live, Non-Replicating Vaccine To Prevent Smallpox And Monkeypox On September 24, 2019, the FDA announced today the approval of Jynneos Smallpox and Monkeypox Vaccine, Live, Non-Replicating, for the prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or [FN32] monkeypox infection. This is the only currently FDA-approved vaccine for the prevention of monkeypox disease. “Following the global Smallpox Eradication Program, the World Health Organization certified the eradication of naturally occurring smallpox disease in 1980. Routine vaccination of the American public was stopped in 1972 after the disease was eradicated in the U.S. and, as a result, a large proportion of the U.S., as well as the global population has no immunity,” said Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research. “Therefore, although naturally occurring smallpox disease is no longer a global threat, the intentional release of this highly contagious virus could have a devastating effect. Today's approval reflects the U.S. government's commitment to preparedness through support for the development of safe and effective vaccines, therapeutics, and other medical countermeasures.” Jynneos will be available for those determined to be at high risk of either smallpox or monkeypox infection. This vaccine is also part of the Strategic National Stockpile (SNS), the nation's largest supply of potentially life-saving pharmaceuticals and medical supplies for use in a public health emergency that is severe enough to cause local supplies to be depleted. The availability of this vaccine in the SNS will help ensure that the vaccine is accessible in the U.S. if needed. Smallpox, which is caused by the variola virus, emerged in human populations thousands of years ago and is a highly contagious and often fatal infectious disease. A person infected with smallpox typically develops a rash characterized by raised pocks on the face and body. The smallpox virus is spread through saliva and droplets from the respiratory tract or by direct or indirect contact with the virus as it is shed from skin lesions. The virus can also be spread through other body fluids and contaminated clothing or bed linen. If a person is infected with smallpox and they are in close contact with others, the virus can spread quickly. Monkeypox, which does not occur naturally in the U.S., is a rare disease caused by infection with monkeypox virus, which causes symptoms similar to, but milder than, smallpox. Monkeypox begins with fever, headache, muscle aches and exhaustion and can be fatal, even though it is typically milder than smallpox. It is transmitted to people from various wild animals, such as rodents and primates. In 2003, the U.S. experienced an outbreak of monkeypox, which was the first time human monkeypox was reported outside of Africa. Jynneos does not contain the viruses that cause smallpox or monkeypox. It is made from a vaccinia virus, a virus that is closely related to, but less harmful than, variola or monkeypox viruses and can protect against both of these diseases. Jynneos contains a modified form of the vaccinia virus called Modified Vaccinia Ankara, which does not cause disease in humans and is non-replicating, meaning it cannot reproduce in human cells. The FDA granted the approval of Jynneos to Bavarian Nordic A/S. FDA Approves First Treatment For Children With Rare Diseases That Cause Inflammation Of Small Blood Vessels On September 27, 2019, the FDA approved Rituxan (rituximab) injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoids (steroid hormones). It is the first approved treatment for children with these rare vasculitis diseases, in which a patient's small blood vessels become inflamed, reducing the amount of blood that can flow through them. This can cause serious problems and damage to organs, most notably the lungs and [FN33] the kidneys. It also can impact the sinuses and skin. “The Rituxan application for pediatric GPA and MPA was approved under a priority review, and with orphan designation, to fulfil an unmet medical need for these rare and serious diseases. Rituxan provides a treatment option that has not existed until now for children who suffer from these diseases,” said Nikolay Nikolov, M.D., associate director for rheumatology of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA's Center for Drug Evaluation and Research. The FDA granted the approval of Rituxan to Genentech. FDA Approves Drug For HIV Prevention On October 3, 2019, the FDA approved Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg) in at-risk adults and adolescents weighing at least 35kg for HIV-1 pre-exposure prophylaxis (PrEP) to reduce the risk of HIV-1 infection from sex, excluding those who have receptive vaginal sex. Descovy is not indicated in individuals at risk of HIV-1 infection from receptive vaginal sex [FN34] because the effectiveness in this population has not been evaluated. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -14- PrEP, or pre-exposure prophylaxis, is an HIV prevention method in which people who do not have HIV take medicine on a daily basis to reduce their risk of getting HIV if they are exposed to the virus. Descovy for PrEP should be used as part of a comprehensive strategy, including adherence to daily administration and safer sex practices, including condoms, to reduce the risk of sexually acquired infections. “PrEP drugs are highly effective when taken as indicated in the drug labeling and can prevent HIV infection,” said Jeffrey Murray, M.D., M.P.H., deputy director of the Division of Antiviral Products in the FDA's Center for Drug Evaluation and Research. “This approval provides more prevention options for certain patients at-risk for acquiring HIV and helps further efforts by the FDA and the U.S. Department of Health and Human Services to facilitate the development of HIV treatment and prevention options to reduce new HIV infections.” Descovy was FDA approved in 2016 in combination with other antiretoviral drugs to treat HIV-1 infection in adults and pediatric patients. The FDA granted the approval of Descovy to Gilead Sciences Inc. FDA Approves New Treatment For Patients With Migraines On October 11, 2019, the FDA approved Reyvow (lasmiditan) tablets for the acute (active but short-term) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults. Reyvow is not indicated for the preventive treatment of migraine. [FN35] “Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans,” said Nick Kozauer, M.D., acting deputy director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research. “We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine.” Migraine headache pain is often described as an intense throbbing or pulsing pain in one area of the head. Additional symptoms include nausea and/or vomiting and sensitivity to light and sound. Approximately one-third of individuals who suffer from migraine also experience aura shortly before the migraine. An aura can appear as flashing lights, zig-zag lines, or a temporary loss of vision. Migraines can often be triggered by various factors including stress, hormonal changes, bright or flashing lights, lack of food or sleep, and diet. Migraine is three times more common in women than in men and affects more than 10% of people worldwide. The FDA granted the approval of Reyvow to Eli Lilly and Company. FDA Approves New Breakthrough Therapy For Cystic Fibrosis On October 21, 2019, the FDA approved Trikafta (elexacaftor/ivacaftor/tezacaftor), the first triple combination therapy available to treat patients with the most common cystic fibrosis mutation. Trikafta is approved for patients 12 years and older with cystic fibrosis who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is estimated to [FN36] represent 90% of the cystic fibrosis population. “At the FDA, we're consistently looking for ways to help speed the development of new therapies for complex diseases, while maintaining our high standards of review. Today's landmark approval is a testament to these efforts, making a novel treatment available to most cystic fibrosis patients, including adolescents, who previously had no options and giving others in the cystic fibrosis community access to an additional effective therapy,” said acting FDA Commissioner Ned Sharpless, M.D. “In the past few years, we have seen remarkable breakthroughs in therapies to treat cystic fibrosis and improve patients' quality of life, yet many subgroups of cystic fibrosis patients did not have approved treatment options. That's why we used all available programs, including Priority Review, Fast Track, Breakthrough Therapy, and orphan drug designation, to help advance today's approval in the most efficient manner possible, while also adhering to our high standards. The FDA remains committed to advancing novel treatment options for areas of unmet patient need, particularly for diseases affecting children.” Cystic fibrosis, a rare, progressive, life-threatening disease, results in the formation of thick mucus that builds up in the lungs, digestive tract, and other parts of the body. It leads to severe respiratory and digestive problems as well as other complications such as infections and diabetes. Cystic fibrosis is caused by a defective protein that results from mutations in the CFTR gene. While there are approximately 2,000 known mutations of the CFTR gene, the most common mutation is the F508del mutation. Trikafta is a combination of three drugs that target the defective CFTR protein. It helps the protein made by the CFTR gene mutation function more effectively. Currently available therapies that target the defective protein are treatment options for some patients with cystic fibrosis, but many patients have mutations that are ineligible for treatment. Trikafta is the first approved treatment that is effective for cystic fibrosis patients 12 years and older with at least one F508del mutation, which affects 90% of the population with cystic fibrosis or roughly 27,000 people in the United States. The FDA granted this application Priority Review, in addition to Fast Track and Breakthrough Therapy Designation. Trikafta also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. Drugs approved under expedited programs are held to the same approval standards as other FDA approvals. Because of Trikafta's benefit to the cystic fibrosis community, the FDA reviewed and approved Trikafta in approximately three months, ahead of the March 19, 2020 review goal date. The approval of Trikafta was granted to Vertex Pharmaceuticals Incorporated, which will receive a Rare Pediatric Disease Priority Review Voucher for developing this therapy. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -15- FDA Approves First Therapy To Treat Patients With Rare Blood Disorder On November 8, 2019, the FDA granted approval to Reblozyl (luspatercept–aamt) for the treatment of anemia (lack of red blood cells) [FN37] in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions. “When patients receive multiple blood transfusions, there is a risk for iron overload, which can affect many organs,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. “Today's approval provides patients with a therapy that, for the first time, will help decrease the number of blood transfusions. This approval is an example of our continued progress for rare diseases and providing important new drugs to patients earlier.” Beta thalassemia, also called “Cooley's anemia,” is an inherited blood disorder that reduces the production of hemoglobin, an iron- containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body and anemia, which can cause pale skin, weakness, fatigue and more serious complications. Supportive treatment for people with beta thalassemia often consists of lifelong regimens of chronic blood transfusions for survival and treatment for iron overload due to the transfusions. People with beta thalassemia are also at an increased risk of developing abnormal blood clots. The FDA granted this application Fast Track designation. Reblozyl also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted approval of Reblozyl to Celegene Corporation. FDA Approves Therapy To Treat Patients With Relapsed And Refractory Mantle Cell Lymphoma On November 14, 2019, the FDA granted accelerated approval to Brukinsa (zanubrutinib) capsules for the treatment of adult patients [FN38] with mantle cell lymphoma who have received at least one prior therapy. “Mantle cell lymphoma usually responds well to initial treatment, but eventually returns or stops responding, and the cancer cells continue to grow. This is a life-threatening condition,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. “Clinical trials showed that 84% of patients saw tumor shrinkage with this therapy. For patients whose disease relapses or becomes refractory, secondary therapies may be successful in providing another remission, and today's approval will provide patients with another treatment option.” Mantle cell lymphoma is a type of non-Hodgkin's lymphoma representing 3-10% of all non-Hodgkin's lymphomas in the United States. By the time it is diagnosed, mantle cell lymphoma has usually spread to the lymph nodes, bone marrow and other organs. In relapsed lymphoma, the disease reappears or grows again after a period of remission, while in refractory lymphoma, the disease does not respond to treatment or responds only briefly. The FDA granted this application Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Brukinsa also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted approval of Brukinsa to BeiGene USA Inc. FDA Approves New Antibacterial Drug To Treat Complicated Urinary Tract On November 14, 2019, the FDA approved Fetroja (cefiderocol), an antibacterial drug for treatment of patients 18 years of age or older with complicated urinary tract infections (cUTI), including kidney infections caused by susceptible Gram-negative microorganisms, who [FN39] have limited or no alternative treatment options. “Today's approval provides an additional treatment option for patients with cUTIs who have limited or no alternative treatment options,” said John Farley, M.D., M.P.H., acting director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research. “A key global challenge the FDA faces as a public health agency is addressing the threat of antimicrobial-resistant infections, like cUTIs. This approval represents another step forward in the FDA's overall efforts to ensure safe and effective antimicrobial drugs are available to patients for treating infections.” Fetroja received the FDA's Qualified Infectious Disease Product (QIDP) designation. The QIDP designation is given to antibacterial and antifungal drug products intended to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act. As part of QIDP designation, Fetroja was granted Priority Review under which the FDA's goal is to take action on an application within an expedited time frame. The FDA granted the approval of Fetroja to Shionogi & Co., Ltd. FDA Approves First Treatment For Inherited Rare Disease On November 20, 2019, the FDA granted approval to Givlaari (givosiran) for the treatment of adult patients with acute hepatic porphyria, a genetic disorder resulting in the buildup of toxic porphyrin molecules which are formed during the production of heme [FN40] (which helps bind oxygen in the blood). “This buildup can cause acute attacks, known as porphyria attacks, which can lead to severe pain and paralysis, respiratory failure, seizures and mental status changes. These attacks occur suddenly and can produce permanent neurological damage and death,” said © 2020 Thomson Reuters. No claim to original U.S. Government Works. -16- Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. “Prior to today's approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks. The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients.” The FDA granted this application Breakthrough Therapy designation and Priority Review designation. Givlaari also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Givlaari to Alnylam Pharmaceuticals. FDA Takes Second Action Under International Collaboration, Approves New Treatment Option For Patients With Chronic Lymphocytic Leukemia [FN41] On November 21, 2019, as part of Project Orbis , a collaboration with the Australian Therapeutic Goods Administration (TGA) and Health Canada, the FDA granted supplemental approval to Calquence (acalabrutinib) for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This new approved indication for Calquence provides a new [FN42] treatment option for patients with CLL or SLL as an initial or subsequent therapy. The FDA's Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA's international partners,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. “We are pleased to continue working alongside our Australian and Canadian colleagues to facilitate new treatment options for patients and the FDA looks forward to working with other countries in future application reviews.” CLL and SLL are similar cancers, but they occur in different areas of the body. CLL occurs mainly in the blood and bone marrow, while SLL occurs mainly in the lymph nodes. Both are cancers of lymphocytes, which are a type of immune cell that helps the body fight infection. Symptoms of CLL or SLL include low red blood cell counts (anemia), low platelet counts, fatigue, enlarged lymph nodes, and a higher risk of infection. In addition to the international collaboration with Australia and Canada, this review used the Real-Time Oncology Review (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application. RTOR, and its accompanying Assessment Aid, facilitated discussions among the regulatory agencies. These applications were approved four months prior to the FDA goal date. The FDA granted this application Priority Review and Breakthrough Therapy designation. The FDA granted approval of Calquence to AstraZeneca. FDA Approves New Treatment For Adults With Partial-Onset Seizures [FN43] On November 21, 2019, the FDA approved XCOPRI (cenobamate tablets) to treat partial-onset seizures in adults. “XCOPRI is a new option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life,” said Billy Dunn, M.D., director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research. “Patients can have different responses to the various seizure medicines that are available. This approval provides an additional needed treatment option for people with this condition.” A seizure is a usually short episode of abnormal electrical activity in the brain. Seizures can cause uncontrolled movements, abnormal thinking or behavior, and abnormal sensations. Movements can be violent, and changes in consciousness can occur. Seizures occur when clusters of nerve cells (neurons) in the brain undergo uncontrolled activation. A partial-onset seizure begins in a limited area of the brain. The FDA granted the approval of XCOPRI to SK Life Science Inc. FDA Approves Novel Treatment To Target Abnormality In Sickle Cell Disease On November 25, 2019, the FDA granted accelerated approval to Oxbryta (voxelotor) for the treatment of sickle cell disease (SCD) in [FN44] adults and pediatric patients 12 years of age and older. “Today's approval provides additional hope to the 100,000 people in the U.S., and the more than 20 million globally, who live with this debilitating blood disorder,” said Acting FDA Commissioner Adm. Brett P. Giroir, M.D. “Our scientific investments have brought us to a point where we have many more tools available in the battle against sickle cell disease, which presents daily challenges for those living with it. We remain committed to raising the profile of this disease as a public health priority and to approving new therapies that are proven to be safe and effective. Together with improved provider education, patient empowerment, and improved care delivery systems, these newly approved drugs have the potential to immediately impact people living with SCD.” Sickle cell disease is a lifelong, inherited blood disorder in which red blood cells are abnormally shaped (in a crescent, or “sickle” shape), which restricts the flow in blood vessels and limits oxygen delivery to the body's tissues, leading to severe pain and organ damage. It is also characterized by severe and chronic inflammation that worsens vaso-occlusive crises during which patients experience episodes of extreme pain and organ damage. © 2020 Thomson Reuters. No claim to original U.S. Government Works. -17- “Oxbryta is an inhibitor of deoxygenated sickle hemoglobin polymerization, which is the central abnormality in sickle cell disease,” said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research. “With Oxbryta, sickle cells are less likely to bind together and form the sickle shape, which can cause low hemoglobin levels due to red blood cell destruction. This therapy provides a new treatment option for patients with this serious and life-threatening condition.” Oxbryta was granted Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. Further clinical trials are required to verify and describe Oxbryta's clinical benefit. The FDA granted this application Fast Track designation. Oxbryta also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Oxbryta to Global Blood Therapeutics. II. Enforcement FDA Takes Action Against 17 Companies for Illegally Selling Products Claiming to Treat Alzheimer's Disease On February 11, 2019, the FDA posted 12 warning letters and 5 online advisory letters issued to foreign and domestic companies that are illegally selling more than 58 products, many that are sold as dietary supplements, which are unapproved new drugs and/ or misbranded drugs that claim to prevent, treat or cure Alzheimer's disease and a number of other serious diseases and health conditions. These products, which are often sold on websites and social media platforms, have not been reviewed by the FDA and are not proven safe and effective to treat the diseases and health conditions they claim to treat. These products may be ineffective, unsafe [FN45] and could prevent a person from seeking an appropriate diagnosis and treatment. “Science and evidence are the cornerstone of the FDA's review process and are imperative to demonstrating medical benefit, especially when a product is marketed to treat serious and complex diseases like Alzheimer's. Alzheimer's is a challenging disease that, unfortunately, has no cure. Any products making unproven drug claims could mislead consumers to believe that such therapies exist and keep them from accessing therapies that are known to help support the symptoms of the disease, or worse as some fraudulent treatments can cause serious or even fatal injuries. Simply put, health fraud scams prey on vulnerable populations, waste money and often delay proper medical care – and we will continue to take action to protect patients and caregivers from misleading, unproven products,” said FDA Commissioner Scott Gottlieb, M.D. “Today's actions are part of the FDA's larger effort to address the booming growth of the dietary supplement industry through the implementation of modern regulatory initiatives that will enable the agency to preserve the balanced vision of the Dietary Supplement Health and Education Act (DSHEA), enacted by Congress 25 years ago. That law sought to achieve the right balance between preserving consumers' access to lawful supplements, promoting innovation in these products, while upholding our obligation to protect the public from unsafe and unlawful products and holding accountable those actors who are unable or unwilling to comply with the requirements of the law. Our newest policy efforts will seize the game-changing opportunity to further strengthen the regulatory framework overseeing dietary supplements and will home in on important steps to both promote industry innovation while upholding the safety of these products as part of our overall commitment to protecting public health.” The products cited in the warning and online advisory letters are unapproved new drugs and/or misbranded drugs that claim to prevent, treat or cure Alzheimer's disease and a number of other serious diseases and health conditions, and have been sold in violation of the Federal Food, Drug, and Cosmetic Act. The products include a variety of product types, such as tablets, capsules and oils. The companies have been asked to respond to the FDA within 15 days of receipt of the letters, stating how the violations outlined in the agency's letters will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure and/or injunction. III. Other Developments FDA Declines to Approve Alkermes Opioid-Based Depression Drug On February 1, 2019, the FDA declined to approve Alkermes Plc's opioid-based depression treatment, citing the need for additional [FN46] data to prove the effectiveness of the drug. The largely expected decision comes months after an advisory panel to the FDA strongly voted against the drug and raised questions on its safety and efficacy. ALKS 5461 is a once-daily pill combining samidorphan and buprenorphine, designed to rebalance brain function that becomes dysregulated in the state of depression. It was developed as an add-on treatment for patients with major depressive disorder (MDD). MDD affects about 16.2 million Americans, of which nearly two-thirds do not respond to currently approved therapies. To date, only three antipsychotic drugs have been approved as add-on treatments for MDD, including AstraZeneca Plc's Seroquel. If approved, Alkermes' treatment would have been the first opioid-based product for depression. Justice Department Says FDA ‘Lacks Jurisdiction’ Over Death-Penalty Drugs © 2020 Thomson Reuters. No claim to original U.S. Government Works. -18- [FN47] On May 3, 2019, the Justice Department posted a new legal opinion that the FDA does not have authority over drugs used in lethal injections. The action came in a legal opinion by the department's Office of Legal Counsel saying that “articles intended for use in capital punishment by a state or the federal government cannot be regulated as ‘drugs' or ‘devices.”’ Therefore, the opinion states, the FDA [FN48] “lacks jurisdiction.” The FDA's role in regulating death-penalty drugs has been hotly disputed in recent years. In 2015, the agency blocked Texas from importing shipments of an anesthetic from an overseas distributor, finalizing the decision two years later. The agency argued the importation was illegal because the drug, sodium thiopental, was not approved in the United States and was improperly labeled. Texas responded by suing the FDA in early 2017, claiming the agency was interfering with the state's responsibility to carry out its law enforcement duties. The legal opinion sides against the FDA and with Texas. It does not appear the opinion will have any immediate effect, however, because the agency is operating under a 2012 court injunction that bars it from allowing the drug into the country. It isn't clear whether the Justice Department will now seek to have the injunction lifted, a move that could spark a long legal tussle. © Copyright Thomson/West - NETSCAN's Health Policy Tracking Service [FN1] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629022.htm [FN2] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629020.htm [FN3] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm629569.htm [FN4] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm630851.htm [FN5] . 2/12/19 Reuters News 19:48:21 [FN6] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm632761.htm [FN7] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm633255.htm [FN8] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634469.htm [FN9] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634837.htm [FN10] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634585.htm [FN11] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm635526.htm [FN12] . https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview [FN13] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm635653.htm © 2020 Thomson Reuters. No claim to original U.S. Government Works. -19- [FN14] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm635906.htm [FN15] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-naloxone-nasal-spray-treat-opioid-overdose [FN16] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-pediatric-patients-lupus [FN17] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-all-genotypes-hepatitis-c-pediatric-patients [FN18] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-anticoagulant-blood-thinner-pediatric-patients-treat- potentially-life-threatening [FN19] . https://www.fda.gov/news-events/press-announcements/fda-approves-innovative-gene-therapy-treat-pediatric-patients-spinal- muscular-atrophy-rare-disease [FN20] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-pi3k-inhibitor-breast-cancer [FN21] . https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-hospital-acquired-and-ventilator-associated- bacterial-pneumonia [FN22] . https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-refractory-multiple-myeloma [FN23] . https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-complicated-urinary-tract-and-complicated-intra- abdominal-infections [FN24] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-lyrica [FN25] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-severe-hypoglycemia-can-be-administered- without-injection [FN26] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-rare-joint-tumor [FN27] . https://www.fda.gov/news-events/press-announcements/fda-approves-third-oncology-drug-targets-key-genetic-driver-cancer-rather- specific-type-tumor [FN28] . https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-patients-rare-bone-marrow-disorder [FN29] . https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibiotic-treat-community-acquired-bacterial-pneumonia [FN30] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-rare-type-lung-disease [FN31] © 2020 Thomson Reuters. No claim to original U.S. Government Works. -20- . https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-glp-1-treatment-type-2-diabetes [FN32] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-live-non-replicating-vaccine-prevent-smallpox-and- monkeypox [FN33] . https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-children-rare-diseases-cause-inflammation- small-blood-vessels [FN34] . https://www.fda.gov/news-events/press-announcements/fda-approves-second-drug-prevent-hiv-infection-part-ongoing-efforts-end-hiv- epidemic [FN35] . https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-patients-migraine [FN36] . https://www.fda.gov/news-events/press-announcements/fda-approves-new-breakthrough-therapy-cystic-fibrosis [FN37] . 2019 WLNR 33819767 [FN38] . 2019 WLNR 34449099 [FN39] . 2019 WLNR 34447547 [FN40] . 2019 WLNR 35073511 [FN41] . https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis [FN42] . 2019 WLNR 35191058 [FN43] . 2019 WLNR 35190882 [FN44] . 2019 WLNR 35551485 [FN45] . https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm631064.htm [FN46] . 2/1/19 Reuters News 21:19:16 [FN47] . https://www.justice.gov/olc/opinion/file/1162686/download [FN48] . 2019 WLNR 14949566 Produced by Thomson Reuters Accelus Regulatory Intelligence 05-Feb-2020 © 2020 Thomson Reuters. 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