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.
“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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