This treatment under study has an innovative mechanism of action that would delay the progression of pulmonary fibrosis. Learn more about how this molecule could improve patients’ quality of life.
Pulmonary fibrosis is a progressive and lethal disease that stiffens the lungs until breathing becomes impossible. Patients’ quality of life is reduced and they can only count on a couple of drugs to delay the inevitable end. For this reason, it is essential to have new treatments that increase their survival.
The Bristol Myers Squibb laboratory is currently studying the molecule BMS-986278, also known by the name “Admilparant”. This has a novel mechanism of action that could improve the outlook for patients with pulmonary fibrosis, both in its idiopathic version (with no apparent cause) and in its progressive interstitial disease version. The clinical trials are open to volunteers from different countries around the world, who can try the new drug without having to stop their current treatment.
Abnormal inflammation and scarring of pulmonary fibrosis
Patients with pulmonary fibrosis suffer from inflammation in the lungs, along with progressive scarring and hardening of lung tissue. As a result, this scarring impedes the exchange of respiratory gases (carbon dioxide for oxygen) in the alveoli — small sacs at the ends of the bronchi responsible for oxygenating the blood.
More specifically, the abnormal scarring process causes an excess buildup of collagen between lung cells, ultimately making the lungs appear like a honeycomb on radiographic images.
So, how does the study medication work? Interestingly, LPA is a growth factor that plays a crucial role in healing lung damage and stimulating the proliferation of cells known as “fibroblasts.” However, when LPA binds to the LPA-1 receptor, it triggers a cascade of fibrotic effects, which prevents lung tissue from regenerating and stops abnormal cells from dying.
Fortunately, the new orally administered pill is an antagonist of the LPA-1 receptor on lung cells, meaning it can block these harmful effects.
In addition, by preventing the LPA factor from binding to the LPA-1 receptor, the drug BMS-986278 disrupts the cellular signals that cause inflammation and scarring of lung tissue. Notably, preliminary studies have already demonstrated that this drug can significantly improve lung function.
Investigational treatment for pulmonary fibrosis
The new oral treatment will be tested in two Phase 3 studies in countries around the world, including the United States, Canada, Mexico, Brazil, Argentina, Colombia, Peru, and Chile. Specifically, the objective of both clinical trials is to evaluate the efficacy, safety, and tolerability of BMS-986278 in 1,185 patients with idiopathic fibrosis (over 40 years of age) and 1,000 patients with progressive pulmonary fibrosis (over 21 years of age).
Patients with each type of fibrosis (idiopathic and progressive) will be separated into 3 groups: one will receive a low dose of the drug; another will receive a high dose; and the last will receive placebo. Patients will be able to continue with their previous treatment simultaneously.
At the end of 52 weeks, the change in forced vital capacity (ability to exhale breathed air, measured by spirometer), the number of patients who experienced syncope (fainting) and other respiratory parameters will be evaluated.
Over 3–4 years, researchers will track fatigue, cough, exacerbations, hospitalizations, disease progression, and adverse effects. By the end, they’ll determine whether BMS-986278’s antifibrinolytic activity is effective and safe for both patient groups.
If you have progressive pulmonary fibrosis, learn more hereBibliographic references
Bristol Myers Squibb. Bristol Myers Squibb’s investigational LPA1 antagonist reduces rate of lung function decline in progressive pulmonary fibrosis cohort of phase 2 study. https://news.bms.com/news/details/2023/Bristol-Myers-Squibbs-Investigation.
Clinical Trials. A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis. https://clinicaltrials.gov/study/NCT0602557886278
Clinical Trials. A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Idiopathic Pulmonary Fibrosis. https://clinicaltrials.gov/study/NCT06003426
Corte TJ, Lancaster L, Swigris JJ, Maher TM, Goldin JG, Palmer SM, et al. Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD). BMJ Open Respir Res. 2021;8(1):e001026. 10.1136/bmjresp-2021-001026 – DOI – PMC – PubMed
Nishioka Y, Araya J, Tanaka Y, Kumanogoh A. Pathological mechanisms and novel drug targets in fibrotic interstitial lung disease. Inflamm Regen. 2024 Jul 19;44(1):34. doi: 10.1186/s41232-024-00345-2. PMID: 39026335; PMCID: PMC11264521.
