Two Next Generation Correctors Advanced into Phase 3 Development for Cystic Fibrosis

Vertex Pharmaceuticals, Inc. announced this morning that VX-659 and VX-445, two next-generation correctors, are being advanced into Phase 3 development as part of two different triple combination regimens for people with cystic fibrosis (CF).

The decision to advance the correctors was based on initial Phase 2 data, including new data from ongoing Phase 2 studies that showed mean absolute improvements in percent predicted forced expiratory volume in one second (ppFEV₁) of up to 13.3 and 13.8 percentage points from baseline through 4 weeks of treatment for the triple combination regimens with VX-659 (400mg QD) or VX-445 (200mg QD), respectively, in people who have a F508del mutation and a minimal function mutation (F508del/Min.).

The 508del mutation typically results in reduced conductance regulator (CFTR) protein activity and a loss of chloride secretion. The combination can lead to impaction of mucus in the airways, gastrointestinal tract, and exocrine organs, and can potentially cause severe clinical consequences including gradual loss of lung function, nutritional deficits, pulmonary exacerbations, and respiratory failure.

It is globally the most rampant CFTR mutation, and approximately 46% of American CF patients are afflicted by it.

The company plans to initiate a Phase 3 program in the first half of 2018 to evaluate VX-659 in triple combination with tezacaftor and ivacaftor, and a Phase 3 program in mid-2018 to evaluate VX-445 in triple combination with tezacaftor and VX-561 as a once-daily regimen, pending additional data, including the Phase 2 data on the combinations of VX-445, tezacaftor and VX-561.

“Together, all the Phase 2 data to date provide further evidence that the addition of a next-generation corrector to tezacaftor and ivacaftor has the potential to provide substantial clinical benefits to patients with one F508del and one minimal function mutation who don’t currently have a medicine to treat the underlying cause of their CF, as well as to provide additional benefits to patients with at least one F508del mutation who are already eligible for CFTR modulator therapies,” said Jennifer Taylor-Cousar, M.D., M.S.C.S., Associate Professor of Medicine and Pediatrics at National Jewish Health, Colorado, and co-chair of Vertex’s Triple Combination Steering Committee in a press release.

Primary objectives in both the Phase 2 studies of VX-445 and VX-659 were safety, tolerability, and efficacy as assessed by mean absolute change in ppFEV₁ from baseline, and secondary endpoints include change in sweat chloride and Cystic Fibrosis Questionnaire-Revised (CFQ-R).

Full data will be presented during the company’s fourth-quarter and full-year 2017 financial results call for investors today, but across both studies, the triple combination regimens were generally well-tolerated, and most of the adverse events (AEs) were mild to moderate in severity. The discontinuation rate due to AEs was low.

“These results support the selection of both the VX-659 and VX-445 triple combination regimens and underscore the potential for these regimens to provide significant clinical benefits for up to 90 percent of people with CF,” said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex.

Vertex is currently finalizing Phase 3 study designs for VX-659 and VX-445 with regulatory agencies. Both Phase 2 data and Phase 3 development strategy will be discussed in the call today, January 31, 2018 at 4:30 p.m. ET.

“We look forward to concluding our discussions with regulators and initiating Phase 3 development in the first half of the year, with the goal of bringing a triple combination regimen to patients as quickly as possible.”

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