Tozorakimab

Roche announced Monday that its investigational anti-ST2 monoclonal antibody astegolimab delivered contrasting results across two pivotal studies in chronic obstructive pulmonary disease (COPD), with the Phase IIb ALIENTO trial meeting its main goal, but the Phase III ARNASA study falling short."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," remarked Levi Garraway, the company's chief medical officer.The 1301-patient ALIENTO and 1375-participant ARNASA trials evaluated the efficacy and safety of astegolimab — dosed every two or four weeks — against placebo in patients with COPD receiving standard maintenance therapies. Both studies enrolled current and former smokers with frequent exacerbations, regardless of eosinophil count. The primary endpoint of the trials was reduction in annualised rates of moderate and severe COPD exacerbations (AER) over 52 weeks.Top-line results from ALIENTO showed a statistically significant 15.4% reduction in AER at 52 weeks with astegolimab administered every two weeks versus placebo. However, in ARNASA, astegolimab recipients achieved only a numerical 14.5% reduction in AER versus placebo, failing to reach statistical significance. Furthermore, findings were generally consistent across secondary endpoints in both studies, and fewer exacerbations than prospectively anticipated were observed.Safety-wise, the antibody’s profile in the pivotal studies aligned with previously reported data, revealing no new safety signals. Detailed results from both trials will be presented at a forthcoming medical conference. While Sanofi and Regeneron's Dupixent (dupilumab) marked the earliest entrant in COPD biologics last year, GSK’s Nucala (mepolizumab) soon followed, securing FDA approval for this indication in May. Meanwhile, besides astegolimab, AstraZeneca's Fasenra (benralizumab) and tozorakimab, Amgen and AstraZeneca’s Tezspire (tezepelumab), and Sanofi and Regeneron's itepekimab are vying for a spot in the biologics COPD space. For more on this, read: Spotlight On: Biologics usher in a new era for COPD.

iStock, Gearstd 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.