Elexacaftor/Ivacaftor/Tezacaftor

The FDA on Friday issued two simultaneous cystic fibrosis approvals for Vertex Pharmaceuticals but included high-level safety warnings for both. The first approval is for Vertex’s “vanza triple” combination, a new product that will be branded as Alyftrek, for use in cystic fibrosis patients aged six years and older. Like some of Vertex’s older products, it is a modulator of the CFTR gene. Its list price is about $370,000 per year, according to SEC documents . Vertex’s second approval is a label expansion for Trikafta, an older CFTR modulator that covers 94 new cystic fibrosis mutations. Alyftrek includes all mutations covered by Trikafta, as well as an additional 31 cystic fibrosis-causing mutations. Both therapies will come with boxed warnings for potential drug-induced liver injury and failure. Previously, Trikafta came with a regular warning and precaution to watch for elevated liver enzymes, but the FDA elevated that to a boxed warning. Alyftrek is made up of three different compounds: vanzacaftor, tezacaftor and deutivacaftor. The combo therapy succeeded in its Phase 3 trials earlier this year, and Vertex used a priority review voucher to reduce the FDA’s review time for Alyftrek to six months. Trikafta brought in $9.8 billion in sales last year, and $7.5 billion through the first three quarters of 2024. It’s not yet clear how or if the new boxed warning will affect Trikafta sales going forward. Vertex is expected to release updated financial guidance during its fourth-quarter earnings call early next year.

– ALYFTREK ™ is approved for patients 6 years and older with at least one responsive mutation, including 31 additional mutations not responsive to other CFTR modulator therapies – – In head-to-head clinical trials, ALYFTREK was non-inferior on ppFEV 1 and further decreased sweat chloride compared to TRIKAFTA ® – BOSTON, MA, USA I December 20, 2024 I Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration (FDA) has approved ALYFTREK (vanzacaftor/tezacaftor/deutivacaftor), a once-daily next-in-class triple combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator for the treatment of cystic fibrosis (CF) in people 6 years and older who have at least one F508del mutation or another mutation in the CFTR gene that is responsive to ALYFTREK. See below for Important Safety Information, including a Boxed Warning. “ALYFTREK is our fifth CFTR modulator to secure FDA approval and represents another significant milestone in our journey to serially innovate and to improve the lives of people living with cystic fibrosis,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “Our north star for more than 20 years has been to address the underlying cause of cystic fibrosis, treat more people with this disease, and bring more people to normal levels of CFTR function — ALYFTREK, with once-daily dosing, efficacy in 31 additional mutations, and lower sweat chloride levels than TRIKAFTA, is another step in achieving this goal.” This approval is based on the most comprehensive Phase 3 pivotal program ever conducted in CF, including more than 1,000 patients across more than 20 countries and more than 200 sites. These data were previously released at the conclusion of the studies and presented at the North American Cystic Fibrosis Conference in September of this year. The Phase 3 studies in people with CF ages 12 years and older met their primary endpoint (non-inferiority on absolute change from baseline in ppFEV 1 compared to TRIKAFTA) and all key secondary endpoints (including absolute change from baseline in sweat chloride [SwCl] compared to TRIKAFTA). In the Phase 3 study of children with CF ages 6-11 years, ALYFTREK demonstrated safety, the primary endpoint. Secondary endpoints, such as absolute change from baseline in ppFEV 1 and absolute change from baseline in SwCl, were presented, supporting the benefit of ALYFTREK in this age group. ALYFTREK was generally well tolerated across all studies. “In Phase 3 clinical trials, across a broad range of genotypes, once-daily ALYFTREK demonstrated non-inferiority to TRIKAFTA in ppFEV 1 response and statistically significant improvement in SwCl, a welcomed advancement for the treatment of CF,” said Claire L. Keating, M.D., Co-Director of the Gunnar Esiason Adult Cystic Fibrosis and Lung Program at Columbia University and investigator in the ALYFTREK clinical trial program. “ALYFTREK has the potential to improve the care of patients with CF.” ALYFTREK is the first, once-daily CFTR modulator. In a recent survey, approximately 75% of physicians reported that more convenient dosing is a very high unmet need for people with CF. Specifically, people with CF will have the added benefit from a once-daily dosing regimen, given the need to take CFTR modulators with fat-containing food. ALYFTREK also offers a potentially transformative option for approximately 150 people with CF in the U.S. with one of 31 mutations who are now eligible for a CFTR modulator for the first time. ALYFTREK was also submitted to global health authorities and is under regulatory review in the European Union, the United Kingdom, Canada, Switzerland, Australia and New Zealand. About Cystic Fibrosis Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 92,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving. Learn more about the importance of sweat chloride (SwCl) in cystic fibrosis. Today Vertex CF medicines are treating over 68,000 people with CF across more than 60 countries on six continents. This represents 2/3 of the diagnosed people with CF eligible for CFTR modulator therapy. ALYFTREK U.S. INDICATIONS ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation. Please click here to see the full U.S. Prescribing Information, including Boxed WARNING for ALYFTREK. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry’s top places to work, including 15 consecutive years on Science magazine’s Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex’s history of innovation, visit www.vrtx.com or follow us on LinkedIn , Facebook , Instagram , YouTube and X . SOURCE: Vertex Pharmaceuticals