US-FDA grants breakthrough therapy status to Bristol Myers Squibb’s investigational LPA1 antagonist to treat progressive pulmonary fibrosis

Bristol Myers Squibb announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for BMS-986278, a potential first-in-class, oral, lysophosphatidic acid receptor 1 (LPA1) antagonist, for the treatment of progressive pulmonary fibrosis (PPF), a devastating, life-threatening illness. Currently, there is only one therapy approved for the treatment of PPF.

The Breakthrough Therapy Designation is based on results from the global, randomized phase 2 study that assessed the safety and efficacy of BMS-986278 treatment versus placebo in people living with idiopathic pulmonary fibrosis (IPF) and PPF. Stable background use of antifibrotics in the IPF cohort and/or select immunosuppressives in the PPF cohort were allowed. Results from the PPF cohort showed that 26 weeks of treatment with a 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 findings were presented at the European Respiratory Society (ERS) 2023 International Congress in September 2023.

Breakthrough Therapy Designation is an FDA program intended to expedite the development and review of medicines for serious or life-threatening diseases with preliminary clinical evidence that the investigational therapy may offer substantial improvement on at least one clinically significant endpoint over available therapies.

“People 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,” said Roland Chen, MD, senior vice president and head, immunology, cardiovascular and neuroscience development, Bristol Myers Squibb. “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.”

In addition to this Breakthrough Therapy Designation for PPF, the US FDA has also previously granted BMS-986278 fast-track designation and orphan drug designation for the treatment of IPF. Bristol Myers Squibb is continuing the development of BMS-986278 with the global phase 3 ALOFT program for PPF (NCT06025578) and IPF (NCT06003426).

BMS-986278 is a potential first-in-class, oral, small molecule lysophosphatidic acid receptor 1 (LPA1) antagonist currently being evaluated as a novel antifibrotic treatment for patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. Increased LPA levels and activation of LPA1 are involved in the pathogenesis of pulmonary fibrosis. A preclinical in vitro and in vivo study found that antagonizing LPA1 may be beneficial in treating lung injury and fibrosis.

The phase 2 study was a global, randomized study in which parallel cohorts of patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) received 30 mg or 60 mg of BMS-986278 or matched placebo orally twice-daily. The study consisted of a 26-week placebo-controlled treatment period, an optional 26-week active treatment extension period and a 4-week post-treatment follow-up period. Patients were permitted to take background antifibrotics in the IPF cohort and background antifibrotics and/or immunosuppressants in the PPF cohort. The primary endpoint was rate of change in percent predicted forced vital capacity (ppFVC) from baseline to Week 26 in the IPF cohort. ppFVC compares the observed FVC to that which is expected for a healthy person of the same age, gender, race and height. Rate of change in ppFVC from baseline through Week 26 in the PPF cohort was a key secondary endpoint. Patients who met prespecified blood pressure reduction criteria were to receive a dose reduction to 10 mg of BMS-986278 or matching placebo twice-daily.

Pulmonary fibrosis is a chronic, life-threatening interstitial lung disease (ILD) that occurs when lung tissue becomes damaged and scarred, impacting how lungs function. Progressive pulmonary fibrosis (PPF) is the preferred term to describe patients who have an ILD with a progressive fibrotic phenotype. Idiopathic pulmonary fibrosis (IPF) is the most common type of progressive fibrosing ILD. As an idiopathic disease, there is no identifiable cause, and as of 2021, more than 700,000 adults are living with IPF globally.

Many people living with PPF and IPF are physically impaired, experience a progressive decline in lung function, have difficulty performing simple daily activities due to breathlessness and require continuous supplemental oxygen to ease the burden of normal breathing.

IPF is a fatal disease with a median survival time of 3-5 years following diagnosis and 5-year survival rate of approximately 45%; PPF has shown a similar prognosis. Innovation in treatment has been limited with few new therapies approved in nearly 10 years.

Optimize Your trial insights with Clival Database.

Are you exhausted from the uncertainty of trial insights pricing? Clival Database ensures the clarity in the midst of the global scenario for clinical trials to you.

Clival Database is one of the best databases that offers an outstanding number of clinical trial data in terms of 50,000+ molecules and from primary regulatory markets as well as new entrants like Indian and Chinese markets.

With Clival, you get accurate positioning of historical sales data, patent database, company profiling, safety & efficacy, and prediction of launch of new innovative molecules helping you to align your research and driving down the cost.

To add value, we further break down our analytics for you so that improving your operational effectiveness; optimizing your clinical trials; and offering you accurate and high-quality data at lowest possible prices becomes possible.

Elevate your trial success rate with the cutting-edge insights from Clival database.

Check it out today and make more informed sourcing decisions! Learn More!