Vertex Faces Choice After Second CF Drug Combo Succeeds in Phase 3

Xconomy Boston — 

An experimental Vertex Pharmaceuticals cystic fibrosis treatment that combines three of the company’s drugs has hit the main goals of two late-stage studies.

It’s the second cystic fibrosis (CF) three-drug cocktail from Boston-based Vertex that has succeeded in two Phase 3 studies. With positive results for both drug combos, the company now must choose which one it will submit for FDA approval.

Following the news, shares of Vertex (NASDAQ: VRTX) dipped 1.4 percent to $185.18 on Wednesday morning.

CF is a genetic disorder caused by mutations to the gene that produces a protein that helps pump water in and out of cells. Without that protein, thick mucus builds up in the lungs, pancreas, and other organs, leading to breathing problems and bacterial infections.

The data released Wednesday are for the experimental Vertex drug VX-445, which was combined with tezacaftor and ivacaftor—two drugs that make up the already-approved Vertex combination treatment for CF marketed as Symdeko. The Phase 3 studies tested this drug cocktail in two groups of CF patients with different genetic mutations.

In preliminary results from those studies, Vertex says the lung function of patients treated with the three-drug cocktail improved by 13.8 percentage points from baseline after four weeks, which was the main goal of the study. The average change in the placebo group was -0.2 percentage points. Vertex says the triple-drug combination was “generally well tolerated” but did not provide additional details.

The Vertex drug ivacaftor (Kalydeco) was the first FDA-approved drug to address the molecular problems underlying CF, but it only works in approximately 5 percent of patients who have a particular genetic mutation. Vertex has been testing combinations of its drugs in an effort to expand the number of CF patients who can be treated. The company has said a three-drug cocktail has the potential to treat up to 90 percent of CF patients.

Last November, Vertex released positive results for two Phase 3 studies testing its first three-drug cocktail, a combination of ivacaftor, tezacaftor, and a different experimental drug, VX-659. In those tests, lung function improved by an average of 14 percentage points after four weeks.

Vertex has said it will choose the better of the two three-drug cocktails to submit for regulatory approval. Because the data for both of the cocktails are similar after four weeks, the company says it will use the final 24-week data to help it decide. Vertex plans to make its choice in the second quarter of this year. At that time, the company says it will disclose 24-week data of the selected drug. A submission to the FDA is expected in the third quarter of this year.

Given the similar clinical trial results for both drug combinations, the choice of which drug to submit to the FDA will likely come down to smaller details, such as side effects or problems that arise from interactions with other drugs a patient may be taking, Stifel analyst Paul Matteis wrote in a research note. Despite the few details about safety, Matteis sees encouraging signs. All of the patients who had finished the study at the time of the interim analysis chose to enroll in the open-label extension study, he noted. The strength of the Phase 3 data mean that Vertex “can own the CF space for the foreseeable future,” Matteis wrote.

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