FDA Grants Breakthrough Therapy Designation to Novel Drug for Progressive Pulmonary Fibrosis

The FDA has granted Breakthrough Therapy Designation to BMS-986278 (Bristol Myers Squibb), a potential first-in-class oral lysophosphatidic acid receptor 1 antagonist (LPA₁), for the treatment of progressive pulmonary fibrosis (PPF). Currently, there is only 1 approved therapy for the treatment of PPF.¹

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BMS-986278 is also being evaluated as a novel antifibrotic treatment for individuals with idiopathic pulmonary fibrosis (IPF). The findings were presented at the European Respiratory 2023 International Congress September 2023.¹

“[Patients] living with pulmonary fibrosis face deteriorating lung function, worsening respiratory symptoms, and reduced quality of life, which can ultimately lead to respiratory failure and death,” Roland Chen, MD, senior vice president and head of Immunology, Cardiovascular and Neuroscience Development at Bristol Myers Squibb, said in a statement. “The FDA’s Breakthrough Therapy Designation underscores the potential of BMS-986278 as an innovative, first-in-class treatment that may redefine the standard of care for progressive pulmonary fibrosis.”¹

The designation is based on results from a phase 2 study (NCT04308681), assessing the safety and efficacy of the drug compared to a placebo for both IPF and PPF. The study was a global, randomized clinical trial with parallel cohorts of those with IPF and PPF who received either 30 mg or 60 mg of BMS-986278, or the matched placebo, twice daily, orally. It had 26 weeks of a placebo-controlled treatment periods, optional 26 weeks of active treatment extension, and 4 weeks of post-treatment follow-up.¹

In the study, investigators could use antifibrotics in the IPF cohort and/or select immunosuppressives in the PPF cohort, according to the statement. The primary endpoint was rate of change in percent predicted forced vital capacity (ppFVC) from baseline to week 26 for those with IPF.

The ppFVC was compared to the FVC observed in healthy individuals of the same age, gender, race, and height. The secondary endpoint included the change in ppFVC from baseline to week 26 in the PPF cohort, according to the statement. For those who met prespecified blood pressure reduction criteria, the dose was reduced to 10 mg of BMS-986278 or a matching placebo twice daily.¹

In the PPF cohort, the findings showed that a twice-daily 60 mg dose of BMS-986278 demonstrated a 69% relative reduction in the rate of decline in percent predicted forced vital capacity compared to the placebo after 26 weeks. In the 30 mg group, there was a 42% relative reduction observed during treatment.²

Furthermore, investigators found that the treatment effect was consistent with and without background therapy, with BMS-986278 being well tolerated. They reported that there were similar rates of adverse events (AEs) compared to the placebo and low discontinuation rates.1 The most frequent AEs included diarrhea, COVID-19, cough, and dyspnea.²

In addition to Breakthrough Designation for PPF, the FDA also granted BMS-986278 fast-track designation and orphan drug designation for the treatment of IPF. Bristol Myers Squibb will continue the development of the drug with the phase 3 ALOFT program for PPF (NCT06025578) and IPF (NCT06003426).¹

References

1. Bristol Myers Squibb announces US FDA Breakthrough Therapy Designation for Investigational LPA1 Antagonist for progressive pulmonary fibrosis. News release. Bristol Myers Squibb. October 24, 2023. Accessed October 24, 2023. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibb-Announces-U.S.-FDA-Breakthrough-Therapy-Designation-for-Investigational-LPA1-Antagonist-for-Progressive-Pulmonary-Fibrosis/default.aspx
2. Bristol Myers Squibb’s investigational LPA1­ antagonist reduces rate of lung function decline in progressive pulmonary fibrosis cohort of phase 2 study. News release. Bristol Myers Squibb. September 9, 2023. Accessed October 24, 2023. https://news.bms.com/news/details/2023/Bristol-Myers-Squibbs-Investigational-LPA1-Antagonist-Reduces-Rate-of-Lung-Function-Decline-in-Progressive-Pulmonary-Fibrosis-Cohort-of-Phase-2-Study/default.aspx