#NACFC2017 – Two Phase 3 Studies of Tezacaftor/Ivacaftor Combo Show Positive Results in CF Patients

Vertex Pharmaceuticals, a clinical-stage biopharmaceutical company, recently announced that two Phase 3 studies evaluating its tezacaftor/ivacaftor combination therapy have shown statistically significant and clinically meaningful improvements in lung function in patients with certain mutations associated with cystic fibrosis (CF).

The first study, called EVOLVE (NCT02347657), was conducted to assess the therapeutic combination in more than 500 patients with two copies of the F508del mutation in the CFTR gene, the most common mutation causing CF.

Results from this 24-week study with CF patients ages 12 and older showed that there were improvements across multiple measures of the disease, including lung function and patient-reported outcomes. Results also showed a reduction in pulmonary exacerbations in patients treated with tezacaftor/ivacaftor compared with patients receiving a placebo. Patients receiving tezacaftor/ivacaftor had a 35% reduction in the annualized rate of pulmonary exacerbations compared to those on the placebo.

“In this study, the tezacaftor/ivacaftor combination demonstrated significant, clinically meaningful improvements in lung function and other measures of cystic fibrosis health status,” Jennifer Taylor-Cousar, MD, co-lead author of the EVOLVE study, said in a press release.

The combination also showed good safety results, with the majority of adverse events reported as mild or moderate. These included pulmonary exacerbation, nasopharyngitis (a common cold), cough, an increase in sputum, and headaches. The rate of adverse events was similar between the placebo and tezacaftor/ivacaftor groups.

“Tezacaftor/ivacaftor was also very well tolerated, which makes it an important potential new option for helping our patients feel better and change the course of their disease. The fact that tezacaftor/ivacaftor will be the basis of triple combination therapy makes this positive data even more exciting for patients with CF and the physicians who care for them,” Taylor-Cousar added.

Results from the EVOLVE study were published in an article titled, “Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del,” in The New England Journal of Medicine.

The second study, called EXPAND (NCT02392234), evaluated the effectiveness of the combination as well as ivacaftor monotherapy (Kalydeco) in patients with one F508del mutation and another mutation that left some residual function of the CFTR protein. All patients in the study were ages 12 or older.

This eight-week study also demonstrated that the combination led to improvements across multiple disease measures, including lung function, in patients receiving both therapies or Kalydeco, compared with patients on a placebo. Lung function improvements were greater in the group receiving tezacaftor/ivacaftor compared to the group receiving only Kalydeco (the mean absolute improvement was 6.8 percentage points for the combo group and 4.7 percentage points for the Kalydeco group compared to a placebo).

“This is an exciting time to be part of cystic fibrosis research as we continue to improve outcomes for patients,” said Steven M. Rowe, MD, MSPH, co-lead author of the EXPAND study and professor of medicine at the University of Alabama at Birmingham.

“These results are particularly exciting because they demonstrate that by addressing the underlying cause of cystic fibrosis, the tezacaftor/ivacaftor combination offers significant benefits for many people with this severe and life-shortening disease, while also offering increased benefit over Kalydeco alone in patients with residual function mutations,” Rowe added.

Results from this study were published in an article titled, “Tezacaftor–Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis,” also in The New England Journal of Medicine.

Results from both studies were also recently included in two oral presentations at the 31st Annual North American Cystic Fibrosis Conference (NACFC), Nov. 2-4, in Indianapolis, Indiana.

“We have made unprecedented progress in the treatment of CF in recent years, but we continue to drive ourselves to deliver even greater benefits for patients today and more new medicines for patients who are still waiting,” said Jeffrey Chodakewitz, MD, executive vice president and chief medical officer at Vertex. “These tezacaftor/ivacaftor results are exciting because they represent the potential to do both.”

Data from these studies were used as the basis for applications for the approval of the tezacaftor/ivacaftor combination by agencies in the United States and Europe. The U.S. Food and Drug Administration (FDA) has granted priority review for the application, and an action date is set for Feb. 28, 2018.