Positive Results from Two Phase 3 Clinical Studies of Tezacaftor (VX-661) and Ivacaftor

Two Phase 3 clinical trials of tezacaftor (VX-661) in combination with ivacaftor (Kalydeco®) showed positive results, Vertex Pharmaceuticals announced today.

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Results released from the first of the large Phase 3 clinical trials of the drug combination demonstrated that people with two copies of the F508del mutation ages 12 and older who received the treatment had significant improvements in lung function -- 4 percentage points compared to placebo -- and in other key measures of the disease, including exacerbations (sudden worsening of symptoms) and quality of life.

Tezacaftor/ivacaftor was well tolerated, with an overall incidence of side effects similar to that seen in the placebo treated group. Additionally, respiratory complications were similar between placebo and treatment groups.

The 24-week study was conducted at over 90 clinical trial sites in North America and Europe. In total, more than 500 people with two copies of the F508del mutation, ages 12 and older participated in the study.

The second of the Phase 3 clinical trials tested the safety and effectiveness of tezacaftor in combination with ivacaftor for people with one F508del mutation and a second CFTR mutation that results in residual function. (Residual function mutations result in some CFTR function being preserved because CFTR protein is present at the cell surface but is either not fully active or not present in sufficient amounts).

The eight-week study showed that, compared with those on placebo, participants with one F508del and one residual function mutation who took the combination treatment improved lung function by 6.8 percentage points. The study also tested ivacaftor without tezacaftor. Participants who only received ivacaftor had a 4.7 percent improvement in lung function compared to placebo.

The residual function mutations eligible for inclusion in the residual function trial were chosen using pre-clinical analysis that identified them as likely to respond to ivacaftor. The list of residual function mutations eligible for inclusion in the trial can be found here. As there are no drugs approved by the U.S. Food and Drug Administration (FDA) to treat the underlying defect of the disease for people with these residual mutations, the more than five percent of people with CF who have these mutations could eventually benefit from modulator therapy.

"These positive results represent a significant step forward in our effort to bring new and more effective treatments targeting the underlying cause of the disease to all people with CF," said Preston W. Campbell, M.D., president and CEO of the CF Foundation. "We have a tremendous amount of momentum right now, and we are determined to build on it to create effective treatments for everyone, regardless of mutation."

Commenting on the long-term significance of the clinical trial results, Michael Boyle, M.D., senior vice president for therapeutics development, said: "Along with the excitement of potential immediate benefit for people with two F508del mutations, these results lay the groundwork for future potent combination therapies which include three different CFTR modulators. We believe these triple combinations will allow us to eventually increase the number benefitting from modulators to over 90 percent of people with CF."

Based on these results, Vertex announced plans to submit a New Drug Application to the FDA in the fall for review and potential approval of the combination treatment for people with two copies of the F508del mutation ages 12 and older as well as for individuals with one copy of the F508del mutation and a residual function mutation ages 12 and older.

For more information, see the Vertex press release.

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