Roche’s hopes of getting its chronic obstructive pulmonary disease (COPD) drug astegolimab to regulators this year have taken a hit after the anti-ST2 monoclonal antibody failed to reduce flare-ups in a phase 3 study.
The Swiss pharma had been evaluating administering astegolimab every two weeks in the phase 2b Aliento trial of 1,301 former and current smokers with a history of frequent COPD exacerbations, as well as the phase 3 Arnasa study of 1,375 patients. The primary endpoint of both trials was the reduction in the annualized rate of moderate and severe COPD exacerbations (AER) over a year of treatment.
While the Aliento trial hit this goal by tying astegolimab to a statistically significant 15.4% reduction in AER, Arnasa only reached a 14.5% reduction, failing that study’s primary endpoint.
The number of exacerbations was “lower than prospectively anticipated in both trials,” Roche admitted in a July 21 release.
The two studies had been the final hurdle for Roche to clear before a planned approval push to U.S. and European regulators later this year, according to a company presentation (PDF) in April. In this morning’s release, the pharma was vague on the future of astegolimab.
“This was the first set of studies in an ‘all-comers’ COPD population, and we will discuss these data with regulatory authorities to evaluate next steps for astegolimab,” Roche Chief Medical Officer Levi Garraway, M.D., Ph.D., said in a statement.
Astegolimab, which Roche originally licensed from Amgen, is designed to stop the binding of interleukin-33 (IL-33) to ST2. The antibody has struggled to make it past phase 2 development, with Roche having previously abandoned attempts to develop the drug for both asthma and COVID patients with pneumonia during the course of 2021.
Last year, AstraZeneca hit a similar setback when tozorakimab, which inhibits IL-33 activities through both the ST2 and RAGE/EGFR signaling pathways, flunked a phase 2 COPD study. The U.K.-based Big Pharma put a brave face on the news, claiming the company was “not worried” about the data and pointing out that the drug is already undergoing a trio of phase 3 studies.
The big news in the COPD space since then is Sanofi and Regeneron’s blockbuster Dupixent becoming the first biologic to be approved for the respiratory condition.