Vertex clears an FDA hurdle with its cystic fibrosis combo

Vertex Chief Medical Officer Jeffrey Chodakewitz

A panel of FDA advisers voted in favor of Vertex Pharmaceuticals' ($VRTX) closely watched combination treatment for cystic fibrosis, looking past some efficacy doubts and setting the stage for a likely approval.

The agency's Pulmonary-Allergy Drugs Advisory Committee voted 12 to 1 in favor of Vertex's treatment, which combines the investigational lumacaftor with ivacaftor, marketed on its own as Kalydeco. The group unanimously backed the drug's safety, as well, passing its recommendations upward to agency regulators. The FDA is not required to follow the votes of its advisers, though it commonly does, and the agency is slated to make a final decision on the combo, dubbed Orkambi, by July 5.

Vertex's new treatment targets the roughly 8,500 patients whose CF is caused by the so-called F508del mutation in their CFTR genes, making up the disease's largest population. Kalydeco, first approved in 2012, is cleared to treat CF patients with different CFTR mutations, a group totaling roughly 2,000, according to Vertex.

In its pivotal trial, Orkambi demonstrated a statistically significant improvement in lung function, a surrogate endpoint for improving CF, but Vertex never authoritatively proved that lumacaftor made a meaningful contribution to Kalydeco alone, panel members said. Asked whether the data demonstrate Orkambi's value over Kalydeco alone, only three panelists said yes, with four voting no and 6 declaring the result indeterminable.

But that isn't enough to negate Orkambi's positive effects compared with placebo, according to the group. A few panelists requested that Vertex conduct a postapproval study comparing its combo to Kalydeco monotherapy to be sure, and it'll be up to the FDA whether to mandate such a trial.

The panel vote is a major positive for Vertex as it looks to expand its dominance in CF. Kalydeco costs about $311,000 on its own, and approval for Orkambi presents the prospect of a costlier drug approved for a larger patient population. And, for a drugmaker recently forced to pull the plug on its once-profitable hepatitis C business, a new cornerstone therapy in CF is an attractive proposition.

"Today's positive recommendation brings the cystic fibrosis community one step closer to potential approval of the first medicine to treat the underlying cause of this disease for many more people," Vertex Chief Medical Officer Dr. Jeffrey Chodakewitz said in a statement. "We look forward to continuing to work with the FDA and other regulatory agencies throughout the world to make Orkambi available to eligible patients as soon as possible."

- read the statement