Vertex Dumps Phase III Cystic Fibrosis Study

August 16, 2016
By Alex Keown, BioSpace.com Breaking News Staff

BOSTON – Shares of Vertex Pharmaceuticals, Inc. are down this morning after the company announced it terminated clinical development of one late stage trial studying the combination of its investigational cystic fibrosis compound VX-661 approved cystic fibrosis drug Kalydeco following the recommendation of an independent data safety monitoring board.

The company said it plans to cease the Phase III trial of VX-661 in combination with Kalydeco (ivacaftor) in people with one copy of the F508del mutation and one copy of a mutation that results in minimal CFTR protein function. The data review committee said there were no safety concerns with the trial, but the results did not warrant further study. Jeffrey Chodakewitz, chief medical officer at Vertex, said in a statement that cystic fibrosis patients with minimal function mutations have a form of the disease which is difficult to treat.

While there are no medicines available for this subgroup, Chodakewitz said the company believes a triple combination regimen may provide this group of people with cystic fibrosis the best chance for treatment. As a result, Chodakewitz said Vertex will begin a Phase I trial that includes a next-generation corrector, VX-661 and Kalydeco later this year.

Cystic fibrosis is a life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia. The median predicted age of survival for a person with cystic fibrosis is between 34 and 47 years, but the median age of death remains in the mid-20s, Vertex said. The disease is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. VX-661 is cystic fibrosis transmembrane conductance regulator (CFTR) corrector.

Although Vertex has halted the combination trial of VX-661 and Kalydeco for the one copy mutation, the company is continuing with other studies for the two medication combination—a study of VX-661 and Kalydeco in people with two copies of the F508del mutation and another trial for patients with one copy of the F508del mutation and one copy of a residual function mutation. Vertex said it completed enrollment this week for the trial of CF patients with two copies and anticipated enrollment of the second trial in September.

Despite the setback in the combination trial, Vertex said it plans to submit a New Drug Application to the U.S. Food and Drug Administration in the second half of 2017 for the combination treatment pending data from the other Phase III programs. The NDA is expected to include data from the study in people with minimal function mutations, the company said.

Vertex has two approved cystic fibrosis drugs on the market, Orkambi and Kalydeco. Orkambi, approved by the U.S. Food and Drug Administration in the summer of 2015, is a combination of Kalydeco and lumacaftor. Orkambi will be used to treat patients with the with the F508del mutation of cystic fibrosis, a mutation the lead drug cannot treat on its own. The F508del mutation is the most common genetic mutation in cystic fibrosis. Analysts have predicted the drug will earn $5 billion by 2018 and finally put Vertex in the black. One reason analysts are so high on the profitability of the drug is its potential to treat more than 20,500 patients in the United States and the European Union, about seven times the reach of Kalydeco, which the company predicts will generate net revenue of $670 to $690 million in revenue in 2016. Last year, Kalydeco received a key boost when President Barack Obama touted its success during the State of the Union Address.

Vertex is slated to release data on another Orkambi trial later this year that is studying the drug in patients ages six to 11.