Drug Development

UPDATED: Vertex shutters a PhIII cystic fibrosis combo study, shares slip

Shares of Vertex slid Monday afternoon after the company said it will scrap one of its late-stage studies for a combination therapy for cystic fibrosis after it failed to pass muster in a futility analysis.

Vertex $VRTX is halting its study of VX-661 and Kalydeco (ivacaftor) in people with one copy of the F508del mutation and one copy of a mutation that results in minimal CFTR protein function (F508del het/min). The study stumbled in its first phase, without an improvement in lung function.

Shares of Vertex slipped 3.4% on the news.

That het/min target represented the largest market opportunity for Vertex with VX-661, according to a note from Leerink’s Geoffrey Porges this morning. But Porges also called it the least likely of the four trials to succeed. Even so, the remaining late-stage studies in the VX-661 studies offer a substantial market opportunity. Notes Porges:

Our analysis and conversations with MEDACorp specialists suggest that Vx-661/Kalydeco could generate an improvement in ppFEV1 in the range of 4-5% in the homozygous delF508 patients, compared to Orkambi’s 2-3%, with greater effects on hospitalizations and exacerbations as well; Vx-661 should be easier to take (less drug-drug interactions, less tolerability and metabolic effects) and have more effect than Orkambi; this success should translate into incremental revenue potential that we estimate to be in the range of ~$485mm, assuming comparable pricing to Orkambi in all markets.

Vertex Chief Medical Officer Jeffrey Chodakewitz

Vertex Chief Medical Officer Jeffrey Chodakewitz

“While we recognize that people with CF with minimal function mutations have a form of the disease that is particularly difficult to treat, we believed it was important to evaluate whether a dual combination of VX-661 and ivacaftor could provide some benefit to these patients given they do not today have a medicine to treat the cause of their disease,” said Vertex Chief Medical Officer Jeffrey Chodakewitz. “These results suggest that a triple combination regimen may provide this group of people with CF the best chance at obtaining a meaningful benefit and we look forward to beginning the first study of a next-generation corrector together with VX-661 and ivacaftor in this group of patients later this year, pending data from our ongoing Phase 1 studies in healthy volunteers.”

VX-661 is Vertex’s second-gen corrector, a successor to the first-gen corrector lumacaftor, included in the drug combination for Orkambi. Two third-gen correctors, VX-152 and VX-440, have been in early-stage studies as Vertex plumbs new approaches that can treat CF better than Orkambi, which has suffered a high dropout rate. The treatment targets the underlying genetic cause of the disease.

The VX-661 program includes four Phase III studies in multiple different groups of people with CF who have at least one copy of the F508del mutation.

Vertex has a $25.4 billion market cap.

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