BMS-986278 declared breakthrough therapy for progressive PF
The FDA designation is based on results from a Phase 2 trial of the investigational therapy
The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to BMS-986278, Bristol Myers Squibb’s investigational therapy for progressive pulmonary fibrosis (PF).
Breakthrough therapy designation is intended to expedite the development and review of medicines for serious or life-threatening diseases. The decision is based on preliminary clinical evidence showing the investigational therapy may improve at least one clinically relevant outcome significantly, compared with available therapies.
“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, ” Roland Chen, MD, said in a press release. Chen is Bristol Myers Squibb’s senior vice president and head of immunology, cardiovascular and neuroscience development.
PF is characterized by tissue scarring, or fibrosis, of the lungs, causing symptoms like shortness of breath, persistent dry and hacking cough, fatigue, and shallow breathing. Progressive PF is the term usually used to refer to patients showing signs of worsening fibrosis, which is difficult to treat and is associated with poor outcomes.
“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,” Chen said.
BMS-986278 is an orally available small molecule that blocks the action of the lysophosphatidic acid receptor 1 (LPA1), a protein in the lungs that plays a role in PF development. Preclinical studies in cell ansd animal model showed that blocking LPA1 could be beneficial in treating lung fibrosis and injury.
The FDA’s decision to grant breakthrough therapy designation to BMS-986278 was based on results from a global Phase 2 clinical trial (NCT04308681) assessing the safety and efficacy of BMS-986278 in 278 people with idiopathic PF (IPF) and progressive PF.
Patients were assigned randomly to receive either 30 or 60 mg of the therapy, or a placebo, taken twice a day, for about six months. Background use of antifibrotics or select immunosuppressive therapies was allowed during the study.
A dose reduction to 10 mg of BMS-986278, or a placebo, twice daily also was allowed if specific blood pressure changes occurred.
A significant relative reduction in lung function decline
Among people with progressive PF, six-month treatment with the 60 mg dose of BMS-986278 led to a 69% relative reduction in the rate of lung function decline compared with placebo, as measured by the percent predicted forced vital capacity (ppFVC). When dose-reduction cases were included, the relative reduction was 74%.
The treatment’s effectiveness was not altered by the presence of background medications.
Moreover, the therapy was well tolerated, with rates of adverse events being similar to placebo. Treatment discontinuation rates by patients also were low.
These findings supported the advancement of BMS-986278’s clinical development to the global Phase 3 ALOFT program for progressive PF (NCT06025578) and IPF (NCT06003426).
The FDA previously granted BMS-986278 fast-track and orphan drug designations for the treatment of IPF, both of which are intended to accelerate the development and regulatory review of therapies for disorders for which there’s an unmet need.
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