VX17-659-103 Efficacy and Safety of VX-659/TEZ/IVA in CF Homozygous

A Phase 3, Randomised, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation (F/F)

CF is caused by decreased quantity and/or function of the Cystic Fibrosis transmembrane conductance protein regulator (CFTR) protein due to mutations in the gene that codes for the CFTR protein. The CFTR protein regulates salt and water absorption and secretion and pH balance in sweat glands and multiple organs, including the lungs, pancreas, and other gastrointestinal organs. The most common disease-causing CFTR mutation is F508del and subjects can either have two copies of the gene, known as homozygous, or one copy, known as heterozygous.

Therapies targeted at improving the function of the protein which is formed as a result of the F508del mutation have shown some positive effects if patients carry two copies of this gene mutation (homozygous).

This study will evaluate the efficacy of VX-659 in triple combination with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with Cystic Fibrosis. Preliminary results from a previous trial with VX-659 indicated a clinical benefit supporting the development of this triple combination. The study population includes male and female subjects with Cystic Fibrosis who are 12 years of age or older, and who are homozygous for the F508del mutation. The study plans to include 100 participants globally, who will be randomised (1:1) to the triple combination arm or triple placebo arm. The study duration is 16 weeks; 4 weeks screening period, 4 weeks for the TEZ/IVA Run-in period, 4 weeks of treatment and 4

weeks for the safety follow-up. The study consists of 8 clinic visits. Study drugs will be taken as a tablet, two in the morning (VX-659/TEZ/IVA) and one in the evening (IVA).