The pivotal Phase III ALOFT-IPF trial of admilparant (BMS-986278) met its primary endpoint at the 60 mg twice-daily dose, demonstrating a statistically significant reduction in lung function decline versus placebo at Week 52 in adults with idiopathic pulmonary fibrosis (IPF), Bristol Myers Squibb (NYSE: BMY) announced. However, the higher 120 mg twice-daily dose failed to achieve statistical significance despite numerically slowing lung function decline.
The approximately 1,255-patient randomized, double-blind, placebo-controlled study evaluated changes in forced vital capacity (FVC), a measure of lung function, over 52 weeks. BMS did not disclose the magnitude of FVC preservation, confidence intervals, or P-values for either dose, leaving the apparent difference between the dose groups unexplained. Both doses were described as well tolerated, with adverse event-related discontinuations low and comparable to placebo, although detailed safety results were not provided. The company plans to discuss regulatory submissions with health authorities following further analysis.
Admilparant is an oral lysophosphatidic acid receptor 1 (LPA1) antagonist designed to inhibit signaling involved in fibroblast activation, tissue scarring, and abnormal lung repair. The Phase III findings build on a previously reported Phase II study in which the 60 mg twice-daily dose reduced the rate of lung function decline by 62% relative to placebo over 26 weeks, using a while-on-treatment analysis. In the treatment-policy analysis, which included data regardless of dose reductions, the relative reduction was 54%.
The treatment landscape has changed since admilparant entered late-stage development. Boehringer Ingelheim's Jascayd (nerandomilast), a preferential PDE4B inhibitor, received US FDA approval in October 2025, joining established antifibrotics nintedanib and pirfenidone. Unlike these treatments, admilparant targets LPA1 signaling, a pathway also being pursued by other developers, including Continuem Therapeutics with PIPE-791.