Vertex Hits Again in CF as First Three-Drug Combo Succeeds in Phase 3

Xconomy Boston — 

Vertex Pharmaceuticals already dominates the landscape of treatments for cystic fibrosis, and its position got even better today.

Vertex (NASDAQ: VRTX) said that a cocktail of three of its cystic fibrosis drugs succeeded in two late-stage studies, bolstering the company’s chances to potentially offer a treatment that addresses up to 90 percent of patients who have the debilitating lung disease. Vertex said the data could support the filing of an FDA approval application.

The regimen Vertex reports on today is a combination of an experimental drug, VX-659; and ivacaftor/tezacaftor, the two parts of the already-approved Vertex CF drug sold as Symdeko. It’s one of two triple drug combinations that the Boston company is currently testing in Phase 3 studies. The company expects to file for approval of the best combination by mid-2019.

Vertex said upon an interim look at the data of both studies—which tested the VX-659/ivacaftor/tezacaftor combo in different subsets of CF patients—its drugs produced a statistically significant improvement in lung function, compared to a placebo, after four weeks of treatment. A positive impact on lung function after four weeks was the study’s main goal.

Specifically, in one 382-patient study, those treated with the Vertex regimen had an average increase of 14 percentage points, versus placebo, after four weeks. In the other 111-patient study, patients’ lung function improved by an average of 10 percent on the Vertex regimen, compared to placebo. Vertex said the combination was “generally well tolerated” but didn’t provide any specifics.

Vertex will now follow these patients for 24 weeks to check on key secondary study goals, like whether patients can avoid what are known as pulmonary exacerbations—acute flare-ups of significant lung problems that can lead to hospital stays.

Shares of Vertex perked up nearly 5 percent on the news.

CF is a genetic disorder that affects more than 70,000 people worldwide, according to the Cystic Fibrosis Foundation. It’s caused by mutations to the gene that produces a protein called CFTR, which helps pump water in and out of cells. Without enough of that protein, the lungs, pancreas, and other organs develop a buildup of thick mucus that can in turn lead to breathing problems and bacterial infections.

For years, the only available CF treatments helped with symptoms. Vertex changed that, starting with the approval of ivacaftor (Kalydeco), the first drug to address the molecular malfunction that underlies the disease, in 2012. But ivacaftor only treats a roughly 5 percent genetic subset of CF patients. Vertex has been steadily broadening the reach of its CF franchise by combining ivacaftor with other drugs it has developed. Since 2015, the company has been cleared to sell two two-drug CF combinations, ivacaftor/lumacaftor (Orkambi) and ivacaftor/tezacaftor (Symdeko). That means, as of now, Vertex can treat approximately 40 percent of CF patients. Its CF franchise generated $782.5 million in sales in the last quarter alone.

A successful three-drug regimen is Vertex’s next big step—and a way for the company to fend off rivals like AbbVie (NYSE: ABBV) and Proteostasis Therapeutics (NASDAQ: PTI), which are developing their own CF cocktails. Vertex has been trying to achieve this by running parallel studies of two different combination. One combo uses VX-659, and the other has the experimental VX-445.

In a research note, Stifel analyst Paul Matteis wrote that the results should ease concerns about competitive pressure from Proteostasis, which recently reported encouraging data from one of its own combinations. Matteis had expected the VX-659 combo to succeed given its results in mid-stage testing, but noted “it is impressive that essentially no regression in benefit was observed in larger pivotal studies.” Should the Vertex regimen win regulatory approval, the CF population it would address represents a “multi-billion dollar opportunity with no targeted therapies approved,” Matteis added.

Enrollment is now complete for the two Phase 3 studies for Vertex’s second triple drug cocktail, which will be tested in the same CF patient groups as the VX-659 combo. Preliminary data are expected early next year.

Vertex will release more safety and efficacy data in late 2019, after it wraps up all of its Phase 3 studies.