Phase 2 study shows 26 weeks of treatment with twice-daily 60 mg dose of BMS-986278 resulted in a 62% relative reduction in the rate of decline in percent predicted forced vital capacity (ppFVC) versus placebo
BMS-986278 was well tolerated with rates of adverse events and treatment discontinuation comparable to placebo. (Credit: Robina Weermeijer on Unsplash)
Bristol Myers Squibb (NYSE: BMY) today announced results from a Phase 2 study evaluating BMS-986278, a potential first-in-class, oral, lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis. The study showed twice-daily administration of 60 mg of BMS-986278 over 26 weeks reduced the rate of decline in percent predicted forced vital capacity (ppFVC) by 62% compared to placebo. Pulmonary fibrosis is a devastating, life-threatening illness, with daily symptoms including coughing, labored breathing and extreme fatigue. These data were presented today at the American Thoracic Society 2023 International Conference held May 19-24, 2023, in Washington, D.C.
In this Phase 2 study, patients were randomized (1:1:1) to placebo, 30 mg or 60 mg BMS-986278 twice-daily for 26 weeks. Two-thirds of patients were on background antifibrotic therapy during the trial. Patients who met prespecified blood pressure reduction criteria were to receive a dose reduction to 10 mg of BMS-986278 or matching placebo twice-daily. Dose reductions due to blood pressure criteria were implemented in 5% (placebo), 8% (30 mg) and 6% (60 mg) of patients. The primary endpoint was rate of change in ppFVC from baseline through 26 weeks as assessed based on two prespecified estimands:
- The treatment policy estimand (similar to an Intention-to-Treat [ITT] analysis) included all observed data regardless of dose reduction and provides an estimate of efficacy with dose reduction as part of the treatment regimen.
- The while-on-treatment estimand included all observed data prior to dose reduction and provides an estimate of efficacy without dose reduction as part of the treatment regimen. A similar number of patients received dose reduction across the placebo (n=5), 30 mg (n=7) and 60 mg (n=6) treatment arms.
A prespecified Bayesian analysis was utilized to provide the probability of a positive treatment difference for BMS-986278 compared to placebo.
Treatment with 60 mg of BMS-986278 led to a 62% relative reduction in the rate of change in ppFVC versus placebo in the while-on-treatment analysis (1.8% mean difference in the rate of change in ppFVC versus placebo [95% CI; 0.2, 3.4]), and a 54% reduction versus placebo in the treatment policy analysis (1.4% mean difference in the rate of change in ppFVC versus placebo [95% CI; −0.1, 3.0]). The Bayesian analysis showed a greater than 95% probability that 60 mg of BMS-986278 was superior compared to placebo in reducing the rate of decline in ppFVC over 26 weeks in both the while-on-treatment and treatment policy estimands. The 30 mg dose was not effective compared to placebo.
BMS-986278 was well tolerated in both treatment arms with rates of adverse events, including rates of gastrointestinal side effects, and treatment discontinuation comparable to placebo. In the placebo, 30 mg and 60 mg arms, adverse events (AEs) occurred in 80%, 76% and 74% of patients, respectively, while serious AEs occurred in 17%, 11% and 11% of patients, respectively. The most frequent AEs in the placebo, 30 mg and 60 mg arms included diarrhea (12%, 11%, 11%), cough (5%, 8%, 11%) and orthostatic hypotension (10%, 8%, 5%). Treatment discontinuation rates due to AEs were comparable to placebo, occurring in 10%, 10% and 7% of patients in the placebo, 30 mg and 60 mg arms, respectively.
“The in-house development of BMS-986278 and progress of our pulmonary fibrosis program are a direct result of our industry-leading drug discovery and development capabilities, underscoring our expertise in disease biology and medicinal chemistry,” said Samit Hirawat, MD, chief medical officer, Bristol Myers Squibb. “These Phase 2 data give us the confidence to initiate our global Phase 3 clinical trial program where we will continue exploring BMS-986278 as a potentially new and meaningful therapeutic option for people with pulmonary fibrosis.”
Source: Company Press Release