Results show 26 weeks of treatment with twice-daily 60 mg dose of BMS-986278 resulted in a 69% relative reduction in the rate of decline in percent predicted forced vital capacity versus placebo

Treatment effect was consistent with or without background therapy and BMS-986278 was well tolerated, with rates of adverse events similar to placebo and low discontinuation rates

These progressive pulmonary fibrosis findings, along with the previously reported idiopathic pulmonary fibrosis cohort results, support continued development of BMS-986278 in Phase 3 ALOFT program

“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 2 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 2 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 immunosuppressives 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).

Rate of Change in ppFVC from Baseline to Week 26 in the PPF Cohort

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 2 study provide us the expertise and confidence to support continued development of BMS-986278 in our global Phase 3 ALOFT program in idiopathic and progressive pulmonary fibrosis.”

Results from the IPF cohort of the Phase 2 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 3 ALOFT (An LPA1 antagonist for pulmonary Fibrosis Trial) program.

Bristol Myers Squibb would like to thank the patients and investigators who were involved in this study.