FDA Wavers on Vertex’s Next Cystic Fibrosis Therapy

Vertex Pharmaceuticals’ Kalydeco/lumacaftor combination therapy may be in danger as regulators question whether it will provide significant improvements in lung function for most cystic fibrosis patients.

The Pulmonary-Allergy Drugs Advisory Committee meets today to debate whether modest improvements in lung function gained in the Kalydeco (ivacaftor)/lumacaftor studies are enough to support approval for the majority of patients with two copies of the Fdel508 mutation, the most common CF mutation.

In clinical studies, those patients showed only 2.7 percent to 3 percent absolute improvement in lung function and 4.3 percent to 5.3 percent improvement relative to the placebo group, the FDA says in briefing materials released ahead of the meeting.

By contrast, patients with G551D in older studies of Kalydeco monotherapy regained between 10.6 percent and 12.5 percent of their lung function. However, Fdel508 patients dosed with Kalydeco in these studies didn’t achieve statistically significant gains in lung function and have been excluded from the drug’s indications thus far. 

The results from the combination therapy trial “raise the question of whether lumacaftor contributes any added benefit … in relation to improvements in lung function and reductions in CF pulmonary exacerbations,” over Kalydeco monotherapy, which has been shown not to improve these patients’ outcomes significantly, the FDA says.

Then again, for the cystic fibrosis community, even small gains in lung function may be enough. “Mean [forced expiratory volume] improvement shown in clinical trials is modest when compared to ivacaftor, but even a modest improvement in FEV, when living with a degenerative disease, is a huge benefit,” says a petition circulating on a major community forum urging the advisory committee to recommend approval.

Kalydeco nabbed its first FDA approval, for about 4 percent of cystic fibrosis patients with the G551D mutation, in 2012.

Since then, nine rarer mutations have been added to the list, and in March the agency extended its use to children as young as two years old.

Read the FDA’s briefing materials at www.fdanews.com/05-11-15-CFbriefing.pdf. — Lena Freund