Admilparant Phase 3 ALOFT-IPF Trial Meets Primary End Point in IPF

Topline results from the phase 3 ALOFT-IPF (NCT06003426) trial found that a 60 mg dose of admilparant, an oral lysophosphatidic acid receptor 1 (LPA₁) antagonist, significantly improved the change in forced vital capacity (FVC) compared with placebo in patients with idiopathic pulmonary fibrosis (IPF).¹

The study evaluated the safety, efficacy, and tolerability of 2 different doses of admilparant 60 mg and 120 mg vs placebo. Admilparant is a potential first-in-class, oral LPA1 antagonist, and the trial data support it as a promising investigational therapy for IPF. Developed by Bristol Myers Squibb (BMS), admilparant is also under investigation for patients with progressive pulmonary fibrosis (PPF) in the fully enrolled phase 3 ALOFT-PPF clinical trial (NCT06025578), with topline results anticipated in early 2027.¹

“Taken together, these topline data reinforce the profile of admilparant as a promising, clinically meaningful investigational therapy for IPF—one that reflects the innovation of targeting the LPA1 pathway as a first-in-class approach,” Cristian Massacesi, MD, executive vice president, chief medical officer, and head of development at BMS, said in a press release. “We also look forward to sharing the topline results from the ALOFT-PPF trial early next year, as we continue working to improve outcomes for patients with pulmonary fibrosis.”

BMS said it will complete a comprehensive evaluation of the data and engage with health authorities to support planned regulatory submissions, with detailed results to be presented at a future medical meeting.¹

Inside ALOFT-IPF: Trial Design, Dosing, and FVC Results

The multicenter, randomized, double-blind, placebo-controlled trial enrolled approximately 1255 adults aged 40 years or older with IPF.¹ Although the complete study is yet to be released, the design and rationale published in May 2025 stated eligibility criteria to be an IPF diagnosis of less than 7 years, a percent predicted FVC (ppFVC) of at least 40%, and a percent predicted diffusing capacity of the lung for carbon monoxide of at least 25%. Background treatment with nintedanib or pirfenidone was permitted.²

Participants were randomized 1:1:1 to receive 60 mg or 120 mg of admilparant, or placebo, twice daily for 52 weeks or longer.¹ Randomization was stratified by background antifibrotic therapy and sex, and the trial used a 2-cohort design that included a smaller initial cohort to evaluate the safety of the 120-mg dose, with spontaneous syncopal episodes as its primary end point. The authors noted that asymptomatic hypotension was observed in 17 of 93 patients (18.3%) who received 60 mg twice daily in the phase 2 trial.²

The primary end point was absolute change in FVC from baseline to week 52. Participants in the 60-mg group demonstrated a statistically significant improvement in absolute change in FVC at week 52 compared with placebo. In the 120-mg group, admilparant slowed the decline of FVC, but the result was not statistically significant.¹

Key secondary end points include time to disease progression and change in the Living with Pulmonary Fibrosis questionnaire cough and dyspnea domain scores at week 52, according to the trial design and rationale.² Although secondary endpoint results were not included in the topline announcement.¹

In the phase 3 trial, admilparant was also well tolerated across both the 60-mg and 120-mg doses. In both admilparant arms, discontinuations due to adverse events were low and similar to placebo.¹

Phase 2 Data Showed Admilparant Delayed Disease Progression in IPF

These data build on a phase 2 trial (NCT04308681) with parallel IPF and PPF cohorts comparing 60 mg of admilparant vs 30 mg of admilparant vs placebo, twice daily for 26 weeks.³ A post hoc analysis of 255 patients with IPF and 114 patients with PPF showed that the 60 mg dose delayed time to disease progression over 26 weeks compared with placebo in both the IPF cohorts.³

In the IPF cohort, 22.6% of patients receiving 60 mg had at least 1 disease progression event when compared with the 39.3% of patients receiving placebo. The difference was driven primarily by fewer relative declines in ppFVC of 10% or more.³ BMS has also reported that 60 mg of admilparant twice daily resulted in a 62% relative reduction in the rate of lung function decline vs placebo in patients with IPF in the phase 2 trial.¹

Approximately 1.4 million people live with IPF globally, according to BMS.¹ Approved antifibrotics pirfenidone and nintedanib have been shown to slow disease progression in IPF. However, neither halts progression, and both are associated with adverse effects that may limit treatment duration.³

“IPF remains one of the most complex and challenging lung diseases to treat, with unpredictable progression, irreversible scarring, and a profound impact on patients’ daily lives,” Fernando Martinez, MD, chair of the ALOFT program clinical steering committee, the Joseph D. Early Chair in Biomedical Research, and interim chair and professor of medicine at UMass Chan Medical School, said in a press release. “These admilparant results represent an important advancement, as there remains a need for therapies that are both effective and tolerable for patients living with IPF.”

References

1. Bristol Myers Squibb announces phase 3 ALOFT-IPF trial evaluating admilparant in adults with idiopathic pulmonary fibrosis met primary endpoint. News release. Bristol Myers Squibb. October 12, 2026. Accessed October 13, 2026. https://news.bms.com/news/details/2026/Bristol-Myers-Squibb-Announces-Phase-3-ALOFT-IPF-Trial-Evaluating-Admilparant-in-Adults-with-Idiopathic-Pulmonary-Fibrosis-Met-Primary-Endpoint/default.aspx

2. Maher TM, Wijsenbeek M, Kreuter M, et al. Design and rationale for a phase 3 trial of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with idiopathic pulmonary fibrosis: ALOFT-IPF. Am J Respir Crit Care Med. 2025;211:A3538. doi:10.1164/ajrccm.2025.211.Abstracts.A3538

3. Kreuter M, Maher TM, Wuyts WA, et al. Effect of admilparant, a lysophosphatidic acid receptor 1 antagonist, on disease progression in pulmonary fibrosis. Chest. 2025;168(3):677-687. doi:10.1016/j.chest.2025.04.003