Roche announced mixed topline results from two pivotal trials evaluating astegolimab, an investigational anti-ST2 monoclonal antibody, in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The Phase IIb ALIENTO study achieved its primary endpoint, while the larger Phase III ARNASA trial did not meet statistical significance despite showing clinical benefit.
Phase IIb Success Contrasts with Phase III Miss
The pivotal Phase IIb ALIENTO study (n=1,301) met its primary endpoint, demonstrating that astegolimab reduced the annualized exacerbation rate (AER) by a statistically significant 15.4% at 52 weeks when administered every two weeks. In contrast, the Phase III ARNASA study (n=1,375) failed to achieve statistical significance for its primary endpoint, showing only a numerical 14.5% reduction in AER at 52 weeks with the same dosing regimen.
Both studies evaluated astegolimab compared to placebo on top of standard of care maintenance therapy in patients with moderate to very severe COPD. The results were generally consistent across secondary endpoints in both trials, though the total number of exacerbations was lower than prospectively anticipated in both studies.
Broad Patient Population Studied
The trials included a comprehensive COPD population encompassing both former and current smokers, regardless of blood eosinophil count, who had a history of frequent exacerbations. This represents the first set of studies in an "all-comers" COPD population, according to Levi Garraway, MD, PhD, Roche's Chief Medical Officer and Head of Global Product Development.
"While COPD remains the third leading cause of death worldwide, patients and families have limited treatment options for managing this debilitating and complex disease," Garraway stated. "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."
Mechanism and Study Design
Astegolimab is an investigational, fully human anti-ST2 monoclonal antibody designed to bind with high affinity to the ST2 receptor, thereby blocking the signaling of IL-33. Both ALIENTO and ARNASA were double-blinded, placebo-controlled, multicenter studies evaluating the efficacy and safety of astegolimab administered every two or every four weeks in COPD patients.
The primary endpoint for both studies was the reduction in the annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period. AER represents the total number of exacerbations—defined as sudden worsening in airway function and respiratory symptoms—occurring over the treatment period, divided by the total number of patient years.
Standard of care maintenance therapy included one of three combinations: inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA); long-acting muscarinic antagonist (LAMA) plus LABA; or ICS plus LAMA plus LABA.
Safety Profile Maintained
The safety profile of astegolimab remained consistent with previously reported data, with no new safety signals identified across both trials. This consistency provides reassurance regarding the drug's tolerability profile in the COPD population.
Regulatory Path Forward
Roche plans to discuss the analysis of both ALIENTO and ARNASA data with regulatory authorities to determine next steps for astegolimab's development program. Detailed results from both studies will be presented at an upcoming medical meeting, providing the scientific community with comprehensive data to evaluate the therapeutic potential of this novel approach to COPD treatment.
