FDA Accepts NDA for VX-445 (Elexacaftor), Tezacaftor, and Ivacaftor Combination Therapy with Priority Review

On August 22, 2019, VCBeat (WeChat ID: vcbeat) learned that Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) announced that the U.S. Food and Drug Administration (FDA) had accepted the New Drug Application (NDA) for the triple-combination therapy of VX-445 (elexacaftor), tezacaftor, and ivacaftor, and granted it Priority Review. The FDA designated March 19, 2020, as the target action date under the Prescription Drug User Fee Act (PDUFA).

This submission is supported by the positive results from two previously disclosed Phase 3 studies in patients with cystic fibrosis (CF): a 24-week Phase 3 study in patients with one F508del mutation and one minimal function mutation, and a 4-week Phase 3 study in patients homozygous for the F508del mutation. Both Phase 3 studies demonstrated statistically significant improvements in lung function (percent predicted forced expiratory volume in 1 second; ppFEV₁), and the triple-combination regimen was generally well tolerated in these studies.

Dr. Reshma Kewalramani, Executive Vice President and Chief Medical Officer of Vertex, stated, “If approved, the triple-combination regimen of VX-445 (elexacaftor), tezacaftor, and ivacaftor would represent a significant advance in the treatment of CF. It would serve as the first CFTR modulator for patients with one F508del mutation and one minimal-function mutation, and provide additional benefits for patients with two F508del mutations. Our goal is to deliver medicines that address the underlying cause of CF to the vast majority of CF patients. We share the urgency felt by CF patients, caregivers, and clinicians, and we are committed to making this innovative CF therapy available to eagerly awaiting patients as soon as possible.”

Cystic Fibrosis (CF) is a rare, life-limiting genetic disorder affecting more than 70,000 individuals worldwide. CF is a progressive multisystem disease that impacts the lungs, liver, gastrointestinal tract, sinuses, sweat glands, pancreas, and reproductive system. It is caused by defects and/or absence of the CFTR protein resulting from specific mutations in the CFTR gene. Children develop CF when they inherit two defective copies of the CFTR gene. Although many different types of CFTR mutations can cause this condition, the vast majority of CF patients have at least one F508del mutation. These mutations can be identified through genetic testing or genotyping assays. The impaired function and absence of the CFTR protein lead to poor regulation of salt and water flow into and out of cells across multiple organs. In the lungs, this results in the accumulation of abnormally thick mucus, causing chronic pulmonary infections and progressive lung damage in many patients, ultimately leading to death.

Vertex, founded in 1989, is a global biotechnology company headquartered in Boston’s Innovation District, USA. The company maintains research and development as well as commercial offices across North America, Europe, Australia, and Latin America. Vertex creates transformative medicines for patients with serious diseases. It has three approved therapies for the treatment of cystic fibrosis (CF) and several ongoing CF clinical and research programs. For other serious conditions, Vertex also boasts a robust pipeline of investigational drugs, including those targeting sickle cell disease, beta-thalassemia, alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, and APOL1-mediated kidney disease.

(Compiled by Tian Shuhang)