Vertex Enrolling Patients with CF in Three, Phase 3 Studies of VX-661 and Kalydeco Combo Therapy

Vertex Pharmaceuticals recently gave an update on its Phase 3 development program, which consists of four studies, on the investigational compound VX-661 in combination with Kalydeco (ivacaftor) as a treatment of patients with cystic fibrosis (CF). The company plans to terminate one study, which is investigating VX-661 plus ivacaftor in people with one copy of the F508del CFTR mutation (CF is caused by mutations in the CFTR gene) and one copy of a mutation that results in minimal CFTR protein function — a hard-to-treat patient group that failed to show treatment efficacy in an interim report.

Vertex also announced that the study assessing the combination therapy in CF patients with two copies of the F508del mutation is fully enrolled.

The VX-661 Phase 3 program now consists of three clinical trials evaluating the combination of VX-661, at 100 mg once daily, plus 150 mg of ivacaftor every 12 hours in groups of CF patients with:

• Two Copies of the F508del Mutation: This fully enrolled study has about 500 patients. Results are expected in early 2017.
• One Copy of the F508del Mutation and a Second Mutation that Results in Residual CFTR Function: Vertex expects to enroll about 200 people with these mutations by September. Data from this study, which includes two eight-week dosing periods, separated by a 8-week washout period, are expected early 2017. For more information on the trial (NCT02392234) and how to participate, please visit this link.
• One Copy of the F508del Mutation and a Second Mutation that Results in a Gating Defect in the CFTR Protein: Enrollment is ongoing, and approximately 200 people are expected to participate in the evaluation of an eight-week treatment schedule. For more information about the trial (NCT02392234) and how to participate, please visit this link.

The two-part study being terminated, in patients with  One Copy of the F508del Mutation and a Second Mutation that Results in Minimal CFTR Function, completed enrollment for Part A in April. The decision to close the study was made after a planned interim futility analysis, conducted by the study’s independent Data Safety Monitoring Board (DSMB), showed that the VX-661 and ivacaftor combination did not result in pre-specified improvements in lung function in these patients. No safety concerns were found. But in light of such results, the board recommended that Vertex stop the study and not initiate enrollment in Part B.

“While we recognize that people with CF with minimal function mutations have a form of the disease that is particularly difficult to treat, we believed it was important to evaluate whether a dual combination of VX-661 and ivacaftor could provide some benefit to these patients, given they do not today have a medicine to treat the cause of their disease,” Jeffrey Chodakewitz, MD, executive vice president and chief medical officer at Vertex, said in a press release of the company’s decision to attempt a study in these patients.

Another clinical investigation for this CF group is planned. “These results suggest that a triple combination regimen may provide … the best chance at obtaining a meaningful benefit and we look forward to beginning the first study of a next-generation corrector together with VX-661 and ivacaftor in this group of patients later this year, pending data from our ongoing Phase 1 studies in healthy volunteers,” Chodakewitz added.

The company plans to submit a New Drug Application (NDA)to the U.S. Food and Drug Administration for VX-661 in combination with ivacaftor in the second half of 2017.