Vertex Pharmaceuticals Inc. announced today that it will seek FDA approval of its CFTR modulator VX-445 (elexacaftor) combined with tezacaftor/ivacaftor (Symdeko®). The VX-445 triple combination was one of two potential triple-combination modulators that Vertex had been testing in late-stage clinical trials. The other, which was not selected, was VX-659 combined with tezacaftor/ivacaftor.
According to the company, Vertex based its selection of VX-445 on a detailed analysis of newly released 24-week clinical trial data, including the drug's safety, tolerability, and drug-drug profiles. In late-stage clinical trials, the VX-445 modulator was associated with a 14.3 percentage point increase in lung function in people with one F508del mutation and one minimal function mutation compared with participants taking a placebo.
Vertex plans to submit a new drug application for VX-445 combined with tezacaftor/ivacaftor to the FDA in the third quarter of 2019. They stated in their release that they will be seeking approval for people ages 12 years and older who have one F508del and one minimal function and in people with two F508del mutations. Approval of the triple-combination drug could, over time, expand therapies which treat the underlying cause of the CF to more than 90 percent of people with the disease.
“Today's announcement represents a significant step forward in our community's quest to treat the underlying cause of CF,” said Preston W. Campbell, III, MD, president and CEO of the Cystic Fibrosis Foundation. “The triple-combination modulator has the potential to transform the treatment of CF for most people with the disease and gives momentum to our ongoing efforts to find effective therapies for all people living with cystic fibrosis.”
Summary of Phase 3 Results for the VX-445 Triple-Combination Modulator
For study participants ages 12 years and older with one F508del and one minimal function mutation (compared to placebo) after 24 weeks:
14.3 percentage point increase in lung function (FEV1)
63 percent reduction in pulmonary exacerbations
-41.8 mmol/L decrease in sweat chloride
+20.2 increase in quality of life measurement (CFQ-R)
The Foundation is committed to finding treatments for the underlying cause of the disease for all people with CF, and significant programs are underway to develop treatments for people with nonsense and rare mutations that will not benefit from CFTR modulators, as well as treatments for the complications of the disease. To learn more about the research the Foundation is supporting in these areas, please visit the Research We Fund section of cff.org.
For additional information regarding today's announcement, please see the Vertex press release.