Modulator treatments for cystic fibrosis: effectiveness and value

Modulator treatments for cystic fibrosis: effectiveness and value

Collection:
Health Policy and Services Research
Author(s):
Tice, Jeffrey A., author
Chapman, Rick M., author
Seidner, Matt, author
Pearson, Steven D., author
Rind, David M., author
Contributor(s):
Institute for Clinical and Economic Review, issuing body.
Publication:
[Boston, Massachusetts] : Institute for Clinical and Economic Review, April 27, 2020
Language(s):
English
Format:
Text
Subject(s):
Cystic Fibrosis -- drug therapy
Cystic Fibrosis Transmembrane Conductance Regulator -- drug effects
United States
Genre(s):
Technical Report
Abstract:
Cystic fibrosis (CF) is an autosomal recessive condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR protein is an ion channel at the cell surface that primarily transports chloride ions across the cell membrane. According to the Cystic Fibrosis Foundation Annual Report, the overall prevalence of CF in the US in 2016 was 30,775. The impact of the disease on patients is profound. The thick secretions cause chronic lung infections, reduced lung function, poor weight gain (due to gastrointestinal dysfunction), diabetes (due to pancreatic damage), and fertility problems. Patients suffer frequent acute pulmonary exacerbations, leading to repeated hospitalizations and long courses of intravenous (IV) antibiotics that require invasive procedures like the placement of ports for IV access and repeated absence from school and work. Because of decreased lung function, patients may have reduced ability to participate in sports and other daily activities. Patients and their families frequently spend several hours every day on treatments intended to help clear the lungs of secretions and thus reduce the likelihood of infections and the risk of declines in pulmonary function. The disease is progressive over time, and patients who become eligible and can obtain one may require lung transplantation to live. Although CF is uncommon, it represents a substantial economic burden. In 2013, CF-related hospital costs alone were estimated to exceed $1.1 billion. This review focuses on the oral triple therapy, Trikafta® (elexacaftor/tezacaftor/ivacaftor, Vertex Pharmaceuticals, Inc.). In addition, we updated our prior review of the three other FDA-approved modulator therapies, all of which are made by the same manufacturer: Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor), and Symdeko® (tezacaftor/ivacaftor). The United States Food and Drug Administration (FDA) approved Trikafta on October 21, 2019 for the treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one copy of the F508del mutation in the CFTR gene (see Table )ES1. The majority (90%) of patients with CF carry at least one copy of the F508del mutation. This mutation leads to the expression of a protein that folds improperly and is not transported to the cell membrane, where it functions. Two of the components of Trikafta, tezacaftor and elexacaftor, help to correct the folding of the protein product from this mutation, thus increasing the amount of the CFTR protein in the cell membrane. The third component of Trikafta, ivacaftor (aka Kalydeco when given alone), increases the flow of ions across the CFTR protein, which helps to alleviate the symptoms of CF. Approximately 27,000 individuals in the United States have CF with genetic mutations that are eligible for treatment with Trikafta (90% of individuals with CF). Of these patients, approximately 17,000 are eligible for treatment under the current FDA label, which limits treatment to patients ages 12 years and older.
Copyright:
Reproduced with permission of the copyright holder. Further use of the material is subject to CC BY license. (More information)
Extent:
1 online resource (1 PDF file (various pagings))
Illustrations:
Illustrations
NLM Unique ID:
101769589 (See catalog record)
Permanent Link:
http://resource.nlm.nih.gov/101769589