Positive results were announced today from two ongoing, late-stage clinical trials of the potential VX-445 triple-combination therapy.
The first study tested VX-445 combined with tezacaftor/ivacaftor (the two drugs that make up Symdeko) in people with cystic fibrosis ages 12 years and older who have one copy of the F508del mutation and one minimal function mutation. Results indicated that after 28 days those who received VX-445 combined with tezacaftor/ivacaftor had a 13.8 percent increase in lung function compared to participants taking a placebo.
The second study included people with CF ages 12 years and older who have two copies of the F508del mutation. The trial compared the effectiveness of VX-445 combined with tezacaftor/ivacaftor to tezacaftor/ivacaftor alone. Participants who were given the triple combination had a 10 percent improvement in lung function after 28 days over those who were given only tezacaftor/ivacaftor without VX-445.
“Today's results reaffirm our belief that a triple-combination therapy will bring significant benefit to the CF community, and has the potential to eventually expand modulator therapy to treat the underlying cause of CF for more than 90 percent of people with the disease,” said Michael P. Boyle, M.D., senior vice president of therapeutics development for the Cystic Fibrosis Foundation. “This would be an incredible step towards our goal of ensuring all people with CF have effective treatments and, ultimately, a cure.”
The VX-445 triple combination is one of two potential triple-combination therapies that have been undergoing late-stage clinical trials by Vertex since 2018. Preliminary results for the other drug candidate, VX-659 in combination with tezacaftor/ivacaftor, were released in November.
After the completion of the Phase 3 trials for both drug candidates (VX-445 triple combination and VX-659 triple combination), Vertex will decide which one they will put forward to the U.S. Food and Drug Administration (FDA) for approval. Vertex has indicated that they will submit a new drug application (NDA) to the FDA for people with two F508del mutations as well as for people with a single F508del and a minimum function mutation during the third quarter of 2019, with a decision from the FDA anticipated in 2020.
If approved by the FDA, the triple-combination would be the first CFTR modulator that could over time benefit the majority of people with CF who have a single copy of the F508del mutation.
Triple-combination therapies represent a significant advance in the treatment of CF. However, the Foundation is steadfast in its commitment to finding treatments for the underlying cause of the disease for all people with CF, and significant programs are underway to address nonsense and rare mutations that will not benefit from CFTR modulators, as well as the development of treatments for 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 the results of the VX-445 clinical trials, please see the Vertex press release.