
Bristol Myers Squibb recently released results from its phase 2 study evaluating BMS-986278, an oral lysophosphatidic acid receptor 1 (LPA1) antagonist in patients who have progressive pulmonary fibrosis (PPF). The investigational, potential first-in-class drug demonstrated a reduced rate of lung function decline in PPF.
The study’s findings, which were announced in September 2023, confirmed that twice-daily administration of 30 mg or 60 mg of BMS-986278 over 26 weeks reduced the rate of decline in percent predicted forced vital capacity (ppFVC) in comparison to the placebo. Results were comparable with or without the addition of background antifibrotics or immunosuppressants.
The global, randomized trial included parallel cohorts of patients with PPF and idiopathic pulmonary fibrosis (IPF). The primary endpoint of the study was total rate of change (baseline to week 26) in ppFVC in the IPF cohort. The secondary endpoint was rate of total rate of change in ppFVC in the PPF cohort and was assessed based on treatment policy estimand and while-on-treatment estimand.
The PPF cohort included 125 patients, all aged 21 years or older and meeting the criteria of progression. 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, and a 74% relative reduction versus placebo in the treatment policy analysis. In the group of patients who received 30 mg, a 42% relative reduction was observed in the while-in-treatment analysis, and a 37% relative reduction was observed in the treatment policy analysis.
“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 to 5 years,” said Tamera J. Corte, MD, clinical trial investigator and consultant respiratory physician and director of interstitial lung disease, department of respiratory medicine, at Royal Prince Alfred Hospital in Sydney. “The phase 2 progressive pulmonary fibrosis results … reinforce the potential of BMS-986278 and highlight advancements in the space as we race to find a potential new standard of care.”
In addition to its consistent efficacy, the drug was well tolerated by individuals across the three groups of the PPF cohort. The most frequent AEs were diarrhea, cough, dyspnea and COVID-19. In the placebo, 30 mg and 60 mg groups, AEs occurred in 78%, 83% and 67% of patients, respectively, while serious AEs occurred in 32%, 10% and 12% of patients, respectively. 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 groups, respectively.
The phase 2 results regarding PPF were presented at the European Respiratory Society (ERS) 2023 International Congress in Milan, Italy, in September. The results pertaining to IPF were previously reported in May 2023 at the American Thoracic Society (ATS) International Congress. In the IPF cohort, treatment with 60 mg of BMS-986278 led to a 62% relative reduction in the rate of change in ppFVC versus placebo.
“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 at Bristol Myers Squibb.
Based on these findings, researchers will continue to evaluate BMS-986278 in the global phase 3 ALOFT program.