The path to market for Roche’s astegolimab became more uncertain after the investigational antibody failed to significantly lower disease exacerbation rates versus placebo in patients with chronic obstructive pulmonary disease.
Roche’s quest to establish itself in the biologics market for chronic obstructive pulmonary disease ran into a late-stage roadblock on Monday when its investigational antibody astegolimab failed to elicit significant improvements in patients with the lung disease. Data in Monday’s release were sparse, with the Swiss pharma reporting only that astegolimab given every two weeks lowered annualized exacerbation rate, the study’s primary endpoint, by 14.5% at 52 weeks.
The late-stage stumble puts Roche further behind powerhouse competitors Sanofi and Regeneron, which are the clear leaders in the space with Dupixent, approved as the first biologic for COPD in September 2024. Sanofi has previously forecast peak annual COPD sales of $5.5 billion for Dupixent.
Roche’s disappointing outcome comes from the Phase III ARNASA trial, which has enrolled some 1,290 patients so far and administered astegolimab every two or every four weeks and compared it against placebo. Roche will report detailed results from ARNASA at an upcoming scientific congress. In the meantime, the pharma will “discuss these data with regulatory authorities to evaluate next steps for astegolimab,” chief medical officer Levi Garraway said in a prepared statement.
Administered subcutaneously, astegolimab is a monoclonal antibody targeting the ST2 receptor, preventing binding of the IL-33 ligand and in turn suppressing a signaling cascade that underpins the immune pathways central to the alveolar damage characteristic of COPD.
Phase IIa data published in 2022 were likewise underwhelming, with astegolimab failing to significantly lower 48-week exacerbation rate versus placebo. Still, the mid-stage trial suggested improvements in overall health and perceived well-being, leading Roche to start two late-stage studies shortly after: ARNASA in December 2022 and a Phase III open-label extension trial in June 2023.
On Monday, Roche also presented Phase IIb data from the ALIENTO trial showing that astegolimab, dosed every two weeks, hit its primary efficacy endpoint, reducing annualized exacerbation rate by 15.4% at 52 weeks. This effect was statistically significant, according to the pharma.
In addition to chasing Sanofi and Regeneron’s Dupixent for a piece of the COPD market, Roche also trails GSK, which is looking to expand its asthma drug Nucala into the indication. A Phase III readout in September 2024 found that Nucala significantly lowered annual rates of moderate or severe COPD exacerbations versus placebo.
AstraZeneca is also advancing a COPD biologic, though it ran its own setback in 2018, after a Phase III flop forced the pharma to abandon plans to expand Fasenra into the indication. The company is now focusing on its late-stage anti-IL-33 antibody tozorakimab, which is currently in Phase III development for COPD.
