AbbVie, Galapagos’ Kalydeco challenger clears phase 2

http://www.fiercebiotech.com/biotech/abbvie-galapagos-kalydeco-challenger-clears-phase-2
Galapagos has posted phase 2 data on the cystic fibrosis drug it is developing with AbbVie. The data suggest the potentiator can play a role in challenging Vertex’s Kalydeco and its follow-up programs, although its place in a planned triple-combination therapy may be taken by a competing candidate.

Investigators gave GLPG1837 to 26 cystic fibrosis patients with the G551D mutation in CFTR, 25 of whom were taking Kalydeco until a week before the start of the study. Participants stopped taking Kalydeco the week before the start of the study, during which time their lung capacity fell 5.4% as measured by ppFEV1.

Subjects then began on a low dose of GLPG1837. The dose was raised twice over the first two weeks of the trial, after which the final 500 mg twice daily regimen was given for 14 days.

By the end of the study, ppFEV1 had returned to levels seen before the participants stopped taking Kalydeco. And participants experienced statistically-significant dose-dependent declines in sweat chloride concentrations. When on 500 mg doses, the mean sweat chloride concentration fell to 66 mmol/L, compared to 98 mmol/L at baseline.

These results suggest GLPG1837 can hold its own against Kalydeco, although differences between the design of the trial and those of Vertex’s drug make it hard to tell how comparable the efficacy is.

In the first two weeks of its trial of Kalydeco, Vertex saw a 9.5% drop in ppFEV1. This bests the return to earlier ppFEV1 levels seen by Galapagos, but the Vertex trial featured treatment-naive patients. The extent to which this affected the change in ppFEV1 is unclear, as are other factors such as the impact of the low starting doses of GLPG1837.

Ultimately, slight differences between the efficacy of GLPG1837 and Kalydeco may have a minimal say in the outcome of the scrap for the cystic fibrosis market. The drugs are one part of planned triple-combination therapies. And, in the case of GLPG1837, its role in the combination is far from assured. Galapagos is set to post data on a once-daily rival for the potentiator position in the combo early next year.

Galapagos is aiming to get its triple-combination into the clinic by the middle of next year. That gives Galapagos and AbbVie time to assess the merits of the potentiators—which boost cell surface chloride transport of CFTR—and the correctors that will make up other two parts of the combo. But it means ceding a head start to Vertex, which has already moved two next-generation correctors into phase 2 triple-combination trials.

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