With 2nd phase 2 win, Bristol Myers Squibb builds case for first-in-class contender in pulmonary fibrosis

After scoring in a more common form of pulmonary fibrosis in May, Bristol Myers Squibb’s lysophosphatidic acid receptor 1 (LPA1) antagonist has turned out positive results in a rarer incarnation of the disease. The clinical win ups the pressure on a pair of entrenched blockbusters in interstitial lung disease—Roche’s Esbriet and Boehringer Ingelheim’s Ofev.

Angling for the first-in-class title, BMS’ investigational LPA1 antagonist BMS-986278 triumphed in a phase 2 study in patients with progressive pulmonary fibrosis (PPF). At 26 weeks, two daily 60-mg doses of BMS' candidate reduced the rate of decline in percent predicted forced vital capacity (ppFVC)—a key measure of lung function in patients with PPF—by 69% versus placebo. 

BMS is sharing the results at the European Respiratory Society 2023 international congress this week.

Notably, 38% of patients in the study received a background antifibrotic therapy like Roche’s pirfenidone, also known as Esbriet, or Boehringer’s nintedanib, which goes by the commercial moniker Ofev.

BMS-986278’s success on top of existing pulmonary fibrosis treatments suggests the drug could have potential as an add-on to established therapies.

Pulmonary fibrosis occurs when the lung tissue becomes damaged and scarred. The disease is characterized by shortness of breath, coughing and fatigue. PPF is less common than its sibling idiopathic pulmonary fibrosis (IPF), though PPF has shown a similar prognosis to IPF. Both diseases are fatal, with a median survival time of three to five years and a five-year survival rate of roughly 45%, BMS said in a press release.

In BMS’ phase 2 study, parallel cohorts of IPF and PPF patients received 30 mg or 60 mg of the company’s LPA1 prospect twice daily over 26 weeks.

Things didn’t go as smoothly for the lower dose of the drug, which only charted a 42% relative reduction in forced vital capacity versus placebo.

However, BMS noted that across doses, treatment was consistent with or without background antifibrotics like Esbriet and Ofev.

BMS-986278’s safety profile was generally well tolerated in both treatment arms, BMS said. Side effect rates were on par with the dummy drug, and discontinuation rates were low, the company added.

Across placebo and both doses of the drug, the most common side effects reported were diarrhea, COVID-19, cough and difficult or labored breathing.

The PPF win comes several months after BMS posted positive phase 2 results on its drug candidate in IPF.

In May, the company reported that a 60-mg dose of BMS-986278 reduced the rate of decline 62% on a measure of ppFVC. The company found that the 30-mg dose was not effective on the same measure.

Given that phase 2 success, BMS plans to begin work on a phase 3 program, the company’s chief medical officer Samit Hirawat, M.D., said earlier this year. On top of Monday’s PPF win, BMS said its drug will now be assessed in the phase 3 ALOFT (An LPA1 antagonist for pulmonary Fibrosis Trial) program.

Both Roche’s and Boehringer’s entrenched antifibrotics have ginned up blockbuster sales over the years.

In 2022, Ofev brought home full-year sales of 3.2 billion euros (about $3.4 billion). Esbriet, for its part, started to suffer from the entry of generics in last year’s second quarter, Roche said in a recent earnings release. The drug posted (PDF) full-year 2022 sales of 718 million Swiss francs (roughly $805 million). Ofev is patent protected until 2029.