Positive EMA opinion for new causal drug in cystic fibrosis

• The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for ALYFTREK in the treatment of people with cystic fibrosis
• Alyftrek is a once-daily triple therapy
• Cystic fibrosis is a rare, life-shortening genetic disease that affects more than 109,000 people worldwide.

Vertex Pharmaceuticals announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for ALYFTREK® (deutivacaftor/tezacaftor/vanzacaftor) for the treatment of individuals aged 6 years and older with cystic fibrosis (CF) who have at least one non-class I mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Alyftrek is a once-daily triple therapy . It consists of vanzacaftor, tezacaftor, and deutivacaftor, active substances belonging to the group of CFTR modulators. These modulators improve the function of the CFTR protein, which is impaired in patients with cystic fibrosis due to genetic mutations.

"Our goal has always been to consistently innovate to help people with CF live healthier, longer lives. If approved, this drug would be indicated for people with CF aged 6 years and older with at least one non-class I mutation, meaning patients would be able to receive a drug that brings their sweat chloride levels closer to normal," said Dr. Carmen Bozic , executive vice president, global drug development and medical affairs and chief medical officer, Vertex.

“CFTR modulators have already revolutionized the way we treat cystic fibrosis, and I am confident that if approved, this drug could expand our treatment options for cystic fibrosis,” said Prof. Marcus A. Mall, MD , Chair of the Department of Pediatric Respiratory Medicine, Immunology, and Intensive Care Medicine and the Cystic Fibrosis Center at Charité - Universitätsmedizin Berlin.

"The results we saw in the two Phase 3 clinical trials of deutivacaftor/tezacaftor/vanzacaftor were encouraging because they demonstrated non-inferiority in ppFEV1 while improving sweat chloride levels compared with ivacaftor/tezacaftor/elexacaftor in combination with ivacaftor," he added.

Cystic fibrosis is a rare, life-shortening genetic disease that affects more than 109,000 people worldwide, including 94,000 in North America, Europe, and Australia. There are more than 1,800 people with cystic fibrosis in Poland.

It is a progressive, multi-organ disease affecting the lungs, liver, pancreas, gastrointestinal tract, sinuses, sweat glands, and reproductive system.

Cystic fibrosis is caused by defective and/or missing CFTR protein, resulting from specific mutations in the CFTR gene. Children must inherit two defective CFTR genes—one from each parent—to develop CF, and these mutations can be identified by a genetic test.

Although there are many different types of CFTR mutations that can cause the disease, most people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing the CFTR protein on the cell surface to malfunction, be deficient, or be absent. The defective and/or absent CFTR protein causes restrictions on the flow of chloride ions (a component of salt) and water to and from the body's cells in various organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections, and progressive lung damage that ultimately leads to death in many patients.

The median age of death is 30, but life expectancy is improving with treatment.

Vertex CF medicines are currently used to treat more than 68,000 people with CF in more than 60 countries on six continents. This means that two-thirds of people with CF who are diagnosed and eligible for CFTR modulator therapy are receiving treatment.

The diagnosis of CF is often made by genetic testing and confirmed by a sweat test (SwCl), which measures CFTR protein dysfunction. The diagnostic threshold for CF is SwCl ≥60 mmol/L, while levels between 30-59 indicate that CF is possible and more testing may be necessary to make a diagnosis. SwCl <30 mmol/L occurs in people who carry one copy of the CFTR gene mutation but have no symptoms of the disease (carriers).

At the population level, higher SwCl levels are associated with more severe disease. Restoration of CFTR function leads to lower SwCl levels. In individuals with CF, mutations in the CFTR gene lead to reduced quantity and/or function of the CFTR channel protein on the cell surface.

Vanzacaftor and tezacaftor are designed to increase the amount of CFTR protein at the cell surface by facilitating the processing and transport of CFTR protein. Deutivacaftor is an enhancer modulator designed to increase the likelihood of the CFTR protein channel being delivered to the cell surface opening to improve the flow of salt and water across the cell membrane.

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