Next Stage of Triple-Combination CFTR Modulator Development Announced

Today Vertex Pharmaceuticals Inc. announced the two next-generation CFTR modulator candidates that will progress into Phase 3 clinical trials.

| 4 min read

The cystic fibrosis transmembrane conductance regulator (CFTR) modulator candidates VX-659 and VX-445 will advance into Phase 3 clinical trials as part of two different triple combination therapies. The decision to proceed with these two modulators was based on data from recent Phase 2 clinical trials that showed these candidates performing better than previous contenders.

The Phase 2 studies for VX-659 and VX-445, for which early results were announced today, examined the effectiveness of each compound in combination with tezacaftor and ivacaftor in individuals with one F508del CFTR mutation and one minimal function mutation. Participants in these clinical trials who took the highest dosage of VX-659 and VX-445 as part of a triple combination saw improvements in their FEV₁ by an average of 13.3 percent and 13.8 percent respectively after four weeks of treatment. Both groups also experienced significant improvements in their sweat chloride levels and their quality of life measurements.

“The research released today underscores the potential of next-generation combination therapies to be significantly more effective than current modulators,” said Michael Boyle, M.D., senior vice president for therapeutics development for the Cystic Fibrosis Foundation. “Importantly, the ability of these potential drugs to treat individuals with a single F508del mutation means that more people than ever before could benefit. This is very exciting news for our community, and we are grateful to those who participated in the clinical trials that made today's announcement possible.”

Vertex Pharmaceuticals Inc. anticipates that the first of the Phase 3 clinical trials for VX-659 in combination with tezacaftor and ivacaftor will begin enrollment in the first half of 2018. The studies will be conducted in people with one F508del mutation and one minimal function mutation, as well as in people with two F508del mutations. Vertex also plans to begin a Phase 3 clinical trial for VX-445 in combination with tezacaftor and the compound VX-561 as a once-daily therapy in people with one F508del and one minimal function mutation, and in people with two F508del mutations, in mid-2018.

“Today's announcement highlights the tremendous potential of the triple combination therapy to address the underlying cause of the disease in more people with CF than ever before,” said Preston W. Campbell, III, M.D., president and CEO of the Cystic Fibrosis Foundation. “We are extremely excited by the prospect of reaching over 90 percent of the CF population with these life-saving modulators and are committed to ensuring that all people with CF will one day have disease-modifying treatments.”

The Cystic Fibrosis Foundation provided $150 million in research funding to Vertex to support its pursuit of treatments that address the underlying defect in CF, including $75 million to develop next-generation candidates currently in clinical development.

Summary of Results:

  • In the early results of the Phase 2 clinical trial of VX-659 in combination with tezacaftor and ivacaftor, the 63 participants in the study with a single F508del mutation who received the highest dose of VX-659 had a 13.3 percent increase in lung function and a decrease in sweat chloride of 51.4 after four weeks of treatment. Improvement in their quality of life score (CFQ-R) was 24.6 points.
  • In the Phase 2 clinical trial of VX-445 in combination with tezacaftor and ivacaftor, the 65 participants in the study with a single F508del mutation who received the highest dose of VX-445 had a 13.8 percent increase in lung function and a decrease in sweat chloride of 39.1 after four weeks of treatment. Improvement in their CFQ-R score was 25.7 points.

For additional information regarding the results of these clinical trials, including the safety and efficacy outcomes, please see the Vertex press release.

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Research | Drug Pipeline
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