Roche's COPD Drug Astegolimab Fails to Meet Primary Endpoint in Phase 3 Trial

Roche's hopes for a new chronic obstructive pulmonary disease (COPD) treatment have been dealt a significant blow as its experimental drug astegolimab failed to meet its primary endpoint in a crucial phase 3 trial. This setback is likely to delay the company's plans for regulatory submissions in the United States and Europe, which were initially slated for later this year.

Phase 3 Trial Results

The phase 3 Arnasa study, involving 1,375 patients, aimed to evaluate the efficacy of astegolimab in reducing the annualized rate of moderate and severe COPD exacerbations (AER) over a one-year treatment period. Despite showing a 14.5% reduction in AER, the results fell short of statistical significance, failing to meet the study's primary endpoint.

This outcome contrasts with the phase 2b Aliento trial, which included 1,301 former and current smokers with a history of frequent COPD exacerbations. The Aliento study demonstrated a statistically significant 15.4% reduction in AER, meeting its primary goal.

Implications and Next Steps

Dr. Levi Garraway, Roche's Chief Medical Officer, commented on the results: "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."

The company noted that the number of exacerbations was "lower than prospectively anticipated in both trials," which may have affected the study outcomes. Roche now faces the challenge of reassessing its development strategy for astegolimab in light of these mixed results.

Broader Context in COPD Treatment Landscape

Astegolimab, an anti-ST2 monoclonal antibody originally licensed from Amgen, has faced challenges in clinical development beyond COPD. Roche previously abandoned efforts to develop the drug for both asthma and COVID-19-related pneumonia in 2021.

The setback for Roche comes in the wake of similar challenges faced by competitors in the COPD space. Last year, AstraZeneca's tozorakimab, which inhibits IL-33 activities through both the ST2 and RAGE/EGFR signaling pathways, also failed to meet its objectives in a phase 2 COPD study.

However, the COPD treatment landscape has seen recent progress with Sanofi and Regeneron's Dupixent becoming the first biologic approved for the respiratory condition, potentially reshaping the competitive environment for future COPD therapies.