Vertex's Kalydeco flunks a Phase III for cystic fibrosis

Vertex Pharmaceuticals' ($VRTX) piecemeal approach to the world's cystic fibrosis sufferers took a hit as Kalydeco failed to meet its primary endpoint in a Phase III trial on patients with one form of the disease, sending the company's shares down as much as 6% premarket on Thursday morning before an eventual rebound.

In a study of 69 CF sufferers with the R117H mutation of the CFTR gene, Kalydeco failed to reach statistical significance in improvement of lung function compared to placebo, the company said. However, the drug did hit primary and secondary endpoints for the 50 patients 18 and older, Vertex said, and the company now plans to meet with the FDA next year to discuss a possible second NDA focusing on that group.

That subset analysis means Kalydeco for R117H patients isn't a lost cause, but even the best-case scenario would lop off a significant portion of the drug's potential market: About 1,111 of CF patients in North America, Europe and Australia carry the R117H mutation, according to Vertex, but only 300 such U.S. patients are over 18.

Last year, the FDA approved Kalydeco in January to treat patients with G551D mutations, who account for about 4% of the CF population. Since then, Vertex has been hammering away at an ambitious program to get the drug, formerly ivacaftor, approved for an array of CF mutations, and the R117H effort is among a fleet of late-stage trials studying Kaldeco on various CFTR defects.

"With each study of ivacaftor, we continue to learn more about this disease and the effect of ivacaftor in patients with different CF mutations, ages and severity of disease," Vertex Chief Medical Officer Robert Kauffman said in a statement. "... While we are disappointed that the study in people with the R117H mutation did not meet its primary endpoint, we are encouraged by the significant improvements in lung function and other measures of CF observed in the subset of patients ages 18 and older who had established lung disease."

But ISI analyst Mark Schoenebaum is preaching patience for Vertex and its banner CF drug. The R117H population amounts to just half of the number of G551D patients already on Kalydeco, Schoenebaum wrote, and the drug's true test will come next year with the arrival of Phase III data from trials studying it in combination with with Lumacaftor (VX-809) on the much more common F508del mutation.

"We do not believe that the results today in R117H patients have any read across to the F508del trials," Schoenebaum wrote in a note to investors. "Perhaps the R117H trial missing the primary endpoint marks the bottom for Vertex?"

- read the announcement

Special Report: 10 top drugs in biopharma's late-stage pipeline - VX-809/VX-661, Vertex

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