Astegolimab gets mixed results in COPD

In the treatment of patients with chronic obstructive pulmonary disease (COPD), use of the anti-ST2 human IgG2 monoclonal antibody astegolimab every 2 weeks helps reduce the frequency of exacerbations compared with placebo in a phase 2b trial but not in a phase 3 trial.

The phase 2b ALIENTO and the phase 3 ARNASA trials involved current or former smokers with COPD and a history of frequent exacerbations, irrespective of baseline blood eosinophils. These patients were randomly assigned to receive astegolimab 476 mg every 2 weeks or every 4 weeks or placebo. Treatment was administered subcutaneous as an adjunct to optimized inhaled maintenance therapy over 52 weeks.

The annualized rate of moderate or severe exacerbations was the primary endpoint.

ALIENTO included 1,301 patients, among whom 433 received astegolimab every 2 weeks, 437 received astegolimab every 4 weeks, and 431 received placebo. ARNASA included 1,375 patients, among whom 459 received astegolimab every 2 weeks, 459 received astegolimab every 4 weeks, and 457 received placebo.

The adjusted rate ratios with astegolimab vs placebo for the primary endpoint were 0.85 (95 percent confidence interval [CI], 0.72–1.00; p=0.049) for the every-2-weeks regimen and 0.93 (95 percent CI, 0.79–1.10; p=0.38) for the every-4-weeks regimen in ALIENTO, and 0.85 (95 percent CI, 0.72–1.01; p=0.068) and 0.82 (95 percent CI, 0.70–0.98; p=0.024) for the respective regimens in ARNASA.

In terms of safety, adverse events (AEs) were comparable across the treatment groups, with AEs occurring in most patients (84 percent in ALIENTO and 85.5 percent in ARNASA). The most common non-COPD AE was nasopharyngitis in ALIENTO and upper respiratory chest infection in ARNASA.

There were 40 patients (3.1 percent) in ALIENTO and 44 (3.2 percent) in ARNASA who died. Across both trials, three deaths (0.1 percent) were considered to be related to treatment by investigators.