PureTech’s only internal drug program has slowed lung function decline in a phase 2 trial in idiopathic pulmonary fibrosis (IPF).
The med, called deupirfenidone, is a deuterated form of Roche’s approved pulmonary fibrosis med Esbriet. PureTech enrolled 257 patients in the trial, who received either 550 mg or 825 mg of deupirfenidone, 801 mg of Esbriet’s ingredient pirfenidone, or placebo three times a day for 26 weeks.
The study hit its primary endpoint by showing that the combined deupirfenidone arms were linked to a slower decline in forced vital capacity (FVC)—a measure of how much air a patient can breathe out—compared to placebo.
Specifically, the 825-mg dose was linked to a 21.5-mL decline in FVC compared to a 112.5-mL decline in the placebo cohort, which PureTech described as a “robust treatment effect of 80.9%.” The 550-mg dose was less effective, showing an FVC decline of 80.7 mL.
Meanwhile, the pirfenidone group showed a 51.6-mL decline in FVC, according to the biotech, which it said was “consistent with previously reported pirfenidone clinical trial data.”
Both doses of deupirfenidone were generally well tolerated, with the 825-mg dose demonstrating a lower percentage than placebo of patients reporting key gastrointestinal adverse events (AEs) like nausea (20.3% to 27.0%, respectively), dyspepsia (14.1% to 22.2%), diarrhea (7.8% to 11.1%) and constipation (4.7% to 6.3%). The only key gastrointestinal AE that bucked this trend was abdominal pain, with 14.1% of patients who received deupirfenidone 825 mg reporting this compared to 7.9% of those on placebo.
Five deaths occurred in the pirfenidone arm, with two fatalities in the placebo arm and one death in each of the deupirfenidone arms, although none of these were deemed treatment-related.
“Our goal in developing deupirfenidone is to offer better outcomes to people living with IPF,” PureTech co-founder and President Eric Elenko, Ph.D., said in the release.
“The adoption and adherence of currently approved antifibrotics has been limited by a tradeoff between efficacy and tolerability, specifically related to gastrointestinal adverse events,” Elenko explained. “This prevents many patients from initiating treatment or maintaining optimal therapeutic doses and, in turn, achieving the best possible outcomes.”
“I could not be more pleased that deupirfenidone showed a favorable tolerability profile at both doses evaluated and—most importantly—has demonstrated the potential to offer patients enhanced efficacy at the higher dose."
CEO Bharatt Chowrira, Ph.D., said that if PureTech could repeat the results in a phase 3 trial, it would “represent a step change in the treatment of IPF.”
Boston-based PureTech is best known for its spinoff companies, including Karuna Therapeutics, which was acquired by Bristol Myers Squibb a year ago. Deupirfenidone is currently listed as PureTech’s only internal program, and the company had at one point also been testing the drug for long COVID before ending that work back in 2022.
Physicians currently rely on Esbriet and Boehringer Ingelheim’s Ofev to manage IPF patients, but those drugs only slow the progression of fibrosis. While many biopharmas have tried and failed to develop more effective treatments in recent years, Boehringer Ingelheim bucked this losing streak in September with a phase 3 win for its PDE4B inhibitor nerandomilast.