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Vertex Announces Positive Phase 1 & Phase 2 Data from Three Different Triple Combination Regimens in People with Cystic Fibrosis Who Have One F508del Mutation and One Minimal Function Mutation (F508del/Min)

BOSTON--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced positive data from Phase 1 and Phase 2 studies of three different triple combination regimens in people with cystic fibrosis (CF) who have one F508del mutation and one minimal function mutation (F508del/Min). These are the first data to demonstrate the potential to treat the underlying cause of CF in these patients, who have a severe and difficult-to-treat type of the disease. Data from the Phase 2 studies in these patients showed mean absolute improvements in percent predicted forced expiratory volume in one second (ppFEV1) of 9.7 and 12.0 percentage points from baseline for the triple combination regimens with VX-152 (200mg q12h) or VX-440 (600mg q12h), respectively. Initial data from a Phase 1 study showed a mean absolute improvement in ppFEV1 of 9.6 percentage points from baseline for the triple combination regimen of VX-659, tezacaftor and ivacaftor in people with one F508del mutation and one minimal function mutation. The company also announced today initial data showing improvements in mean absolute ppFEV1 of 7.3 and 9.5 percentage points when VX-152 or VX-440 was added in people with two copies of the F508del mutation, who were already receiving tezacaftor and ivacaftor. Vertex will host a conference call for investors today, July 18, 2017 at 5:00 p.m. EDT, to discuss these results.

The triple combination regimens were generally well tolerated across all three studies, and the majority of adverse events were mild to moderate in severity. Across the studies, the discontinuation rate due to adverse events was low.

“These safety and efficacy data are clear and compelling, indicating significant potential benefit for people with CF from each of these three different triple combination regimens,” said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex. “We will be collecting and evaluating additional data from these and other studies and will make a decision on which regimen(s) to take forward into pivotal program(s), which we expect to begin in the first half of 2018.”

Vertex has established a Steering Committee of global CF experts and clinical trial investigators to support the design, conduct and execution of the triple combination pivotal study program. This committee is co-chaired by Steven M. Rowe, M.D., M.S.P.H., Professor of Medicine, Pediatrics, and Cell, Developmental and Integrative Biology, Director of the Gregory Fleming James Cystic Fibrosis Research Center, Nancy and Eugene Gwaltney Endowed Chair for Medical Research, University of Alabama at Birmingham, and Jennifer Taylor-Cousar, M.D., Associate Professor, Departments of Medicine and Pediatrics, Pulmonary Divisions, Medical Director of Clinical Research Services and Co-Director and Director of the CF Therapeutics Development Network, Adult CF Program, National Jewish Health, Colorado.

“Patients with minimal function mutations have been waiting for a medicine to treat the underlying cause of their disease, which makes these data showing pronounced improvements in lung function particularly important,” said Dr. Rowe. “It’s also encouraging to see that the addition of a next-generation corrector may lead to substantial additional benefits for patients with two copies of the F508del mutation, who were already receiving tezacaftor and ivacaftor.”

Next Steps

Vertex has advanced four next-generation correctors in parallel with the goal of developing the best triple combination regimen or regimens for people living with CF.

Vertex has accelerated the development programs for VX-445 and VX-659. A VX-445 Phase 2 study is underway and a VX-659 Phase 2 study will begin in early August. VX-445 and VX-659 will be evaluated in triple combination with tezacaftor and ivacaftor in people with one F508del mutation and one minimal function mutation and will be evaluated in people with two copies of the F508del mutation who are already receiving tezacaftor and ivacaftor. Data from both of these Phase 2 studies are expected in early 2018.

Pending additional data from these Phase 2 studies and the ongoing studies of VX-152 and VX-440 and discussions with regulatory agencies and the Steering Committee, Vertex plans to initiate pivotal development of one or more triple combination regimens in the first half of 2018.

About the VX-440 Phase 2 Study

This randomized, double-blind Phase 2 study is evaluating VX-440 (200mg and 600mg q12h) in combination with tezacaftor and ivacaftor in two different groups of people with CF ages 18 and older – those who have one F508del mutation and one minimal function mutation, and in those who have two copies of the F508del mutation. Minimal function mutations are those that result in little-to-no functioning CFTR protein and are not responsive to ivacaftor, tezacaftor or the combination of ivacaftor and tezacaftor. The primary objectives for the study are safety, tolerability and efficacy as assessed by mean absolute change in ppFEV1 from baseline. Secondary endpoints include change in sweat chloride and Cystic Fibrosis Questionnaire-Revised (CFQ-R).

Overall Safety Data: In the study, the triple combination regimen was generally well tolerated. The majority of adverse events were mild or moderate. The most common adverse events (>10%), regardless of treatment group, were infective pulmonary exacerbation, cough, sputum increased and diarrhea. There was one discontinuation due to an adverse event in the triple combination treatment groups (elevated liver enzymes >5x upper limit of normal in the VX-440 600mg group) and one in the control groups (respiration abnormal and sputum increased). One additional patient treated with the triple combination had elevated liver enzymes (>8x upper limit of normal in the VX-440 600mg group), which were observed on the final day of...


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