Vertex’s Orkambi CF Combo Therapy Wins Approval From Advisory Panel

May 20, 2015

An FDA advisory panel last week voted 12 to 1 in favor of approving Vertex Pharmaceuticals’ combination cystic fibrosis therapy Orkambi for patients 12 years and older with two copies of the F508del mutation, paving the way for its likely approval by a July 5 PDUFA date.

If the FDA follows the panel’s recommendation and approves Orkambi, it would be Vertex’s second cystic fibrosis drug — after Kalydeco (ivacaftor), which was approved in 2012 — and the second globally to specifically target a genetic mutation linked to the disease, rather than just treating the symptoms. F508del is the most common mutation, affecting about half of all cystic fibrosis patients.

The debate on the drug was intense. Members of the Pulmonary-Allergy Drugs Advisory Committee unanimously agreed that Orkambi’s (Kalydeco/lumacaftor) safety profile is good, and that any adverse events such as elevated liver enzymes and cataracts can be managed with monitoring and corticosteroids.

There was less agreement on the drug’s efficacy data, with seven of the 13 panelists saying the data from the Kalydeco monotherapy studies wasn’t strong enough to make a clear determination of lumacaftor’s specific benefit.

However, several panelists pointed out that even a small gain of 3 percent lung function, as seen in the Orkambi trials, is significant given that many patients with these mutations lose that amount of lung capacity each year.

The panel’s consumer representative was the sole holdout, arguing that the efficacy data wasn’t strong enough to support approval. That echoed the FDA’s briefing documents, which raised doubts about whether the modest increases in lung function gained by patients with the F508del mutation in two Phase III trials of Orkambi constitute meaningful clinical benefit. — Lena Freund