In what was widely expected given the warnings from the company in recent months, Vertex ($VRTX) has halted a trial that combined its approved med Kalydeco (ivacaftor) together with its experimental treatment VX-661 in cystic fibrosis (CF).
Other trials for VX-661, its lead pipeline drug, are still ongoing, but it has stopped its combo Phase III study in a small subpopulation of patients with one copy of the F508del mutation and one copy of a mutation that results in minimal CFTR protein function (F508del het/min).
This comes after an independent Data Safety Monitoring Board, which said that the results it had seen did not warrant further tests. Vertex noted that there were not however any safety issues coming out of the study.
The company will push on with other studies for the two meds, though, and said that this week it had just finished enrollment for the study of VX-661 and Kalydeco in people with two copies of the F508del mutation (F508del homozygous).
Another trial, which will enroll people with one copy of the F508del mutation and one copy of a residual function mutation, should also be completed by September, the company said in a statement.
“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 Jeffrey Chodakewitz, EVP and chief medical officer at Vertex.
“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 I studies in healthy volunteers.”
Vertex said despite this setback, it still expects to submit an NDA to the FDA for a Kalydeco/VX-661 cocktail treatment in the second half of 2017, pending data from its remaining Phase III trials. The NDA will include data from the study in people with minimal function mutations, the company added.
Vertex already has a combo CF treatment on the market in the form of Orkambi (ivacaftor and lumacaftor), which has a U.S. license for CF in patients who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene.
Analysts at Jefferies did not see the dropping of one of the studies as terminal to its CF pipeline, saying in a note to clients, “We believe expectations were low [for this subpopulation], and this does not change our overall positive CF franchise view.”
But Jefferies said that the “(f)ew details in PR or from company discussions make it difficult to have any increased clarity on '661's ultimate likelihood of success in other populations, though timelines for those other Phase IIIs appear intact.
“Vertex is still not disclosing the bar for this interim analysis, so it is difficult to know if any small signals activity were observed, though we believe if there were any lung function benefits worth following up on the study would likely have proceeded to part 2.”
Vertex traded down 3.2% after hours last night when the news was released, having ended the normal day’s trading nearly 1% up.