BMS 986278 reduces rate of lung function decline in progressive pulmonary fibrosis cohort of phase II study

The study showed that 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 69% compared to placebo (overall, 38% of patients in the study received background antifibrotic therapy). These data will be presented during the Abstracts Leading to Evolution in Respiratory Medicine Trials (ALERT) session 1 at the European Respiratory Society (ERS) 2023 International Congress held September 9-13 in Milan, Italy.

“People living with pulmonary fibrosis are in urgent need of new treatment options for this devastating disease, which has a median overall survival of 3-5 years,” said Professor Tamera J. Corte, clinical trial investigator and Consultant Respiratory Physician and Director of Interstitial Lung Disease, Department of Respiratory Medicine, Royal Prince Alfred Hospital?. “The Phase II progressive pulmonary fibrosis results, which demonstrate consistent efficacy with or without background antifibrotic therapy and a favorable tolerability profile, reinforce the potential of BMS 986278 and highlight advancements in the space as we race to find a potential new standard of care.”

This Phase II study was a global, randomized trial in which parallel cohorts of patients with idiopathic pulmonary fibrosis (IPF) and PPF received 30 mg or 60 mg of BMS 986278 or matched placebo orally twice-daily for 26 weeks. Stable background use of antifibrotics in the IPF cohort and/or select immuno-suppressives in the PPF cohort were allowed. The primary endpoint of the study was rate of change in ppFVC from baseline to Week 26 in the IPF cohort. Rate of change in ppFVC from baseline through 26 weeks in the PPF cohort was a key secondary endpoint of the study and was assessed based on two prespecified estimands (treatment policy estimand and while-on-treatment estimand).

In the PPF cohort, treatment with 60 mg of BMS 986278 led to a 69% relative reduction in the rate of change in ppFVC versus placebo in the while-on-treatment analysis (treatment difference versus placebo 2.9%; 95% CI: 0.4, 5.5), and a 74% relative reduction versus placebo in the treatment policy analysis (3.2%; 95% CI: 0.7, 5.6). In the 30 mg group, a 42% relative reduction was observed in the while-on-treatment analysis (1.8%, 95% CI: -0.9, 4.4), and a 37% relative reduction was observed in the treatment policy analysis (1.6%; 95% CI: ?1.0, 4.1). The treatment effect was consistent in the presence or absence of background antifibrotics and usual interstitial pneumonia (UIP) pattern (in the placebo, 30 mg and 60 mg groups, 41%, 38% and 36% of patients were on background antifibrotic therapy, respectively; UIP pattern was present in 51%, 55% and 50% of patients in the placebo, 30 mg and 60 mg groups, respectively).

BMS 986278 was well tolerated in both treatment arms of the PPF cohort, with rates of adverse events (AEs) similar to placebo and low discontinuation rates. In the placebo, 30 mg and 60 mg arms, AEs occurred in 78%, 83% and 67% of patients, respectively, while serious AEs occurred in 32%, 10% and 12% of patients, respectively. The most frequent AEs in the placebo, 30 mg and 60 mg arms included diarrhea (15%, 15%, 7%), COVID-19 (5%, 15%, 14%), cough (10%, 8%, 12%) and dyspnea (15%, 5%, 0%). Treatment discontinuation rates due to AEs were highest in the placebo arm, occurring in 15%, 3% and 0% of patients in the placebo, 30 mg and 60 mg arms, respectively.

“The results from this innovative study investigating idiopathic and progressive pulmonary fibrosis give us unprecedented insights that will inform our scientific understanding of pulmonary fibrosis and the role of LPA1 inhibition,” said Jonathan Sadeh, MD, MSc, senior vice president of Immunology Development, Bristol Myers Squibb. “Our industry-leading drug discovery and development capabilities and collective results from this Phase II study provide us the expertise and confidence to support continued development of BMS 986278 in our global Phase III ALOFT program in idiopathic and progressive pulmonary fibrosis.”

Results from the IPF cohort of the Phase II study were previously presented at the American Thoracic Society (ATS) International Conference in May 2023, showing a 62% relative reduction in the rate of decline in ppFVC with 60 mg BMS 986278 versus placebo with or without background therapy..

BMS 986278 will now be evaluated in the global Phase III ALOFT (An LPA1 antagonist for pulmonary Fibrosis Trial) program.