2 global trials show mixed results for astegolimab for treating COPD
Developer Genetech to discuss data with regulators to decide next steps
Genentech has announced mixed top-line results from two global clinical trials testing its treatment candidate astegolimab in people with moderate to very severe chronic obstructive pulmonary disease (COPD).
Both one-year trials aimed to demonstrate that the therapy was superior to a placebo at reducing the annual rate of moderate and severe COPD exacerbations — periods when symptoms suddenly worsen — among patients.
In the Phase 2b ALIENTO study (NCT05037929), there was a statistically significant reduction in exacerbation risk with astegolimab relative to the placebo, the data showed. However, in the Phase 3 ARNASA study (NCT05595642), the group difference in exacerbation risk failed to reach statistical significance, the company reported.
“While COPD remains the third leading cause of death worldwide, patients and families have limited treatment options for managing this debilitating and complex disease,” Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of global product development, said in a company press release, which noted that detailed results from both trials will be shared at a future meeting.
“We will discuss these data with regulatory authorities to evaluate next steps for astegolimab,” Garraway said.
Astegolimab is an antibody-based therapy designed to block the activity of interleukin-33 (IL-33), a signaling molecule that’s thought to be involved in driving lung inflammation in COPD. It’s given by subcutaneous, or under-the-skin, injection.
An earlier Phase 2a trial dubbed COPD-ST2OP (NCT03615040) had tested astegolimab against a placebo in more than 100 COPD patients. Those results showed that exacerbation rates were lower among astegolimab-treated patients. However, the difference wasn’t statistically significant, meaning that the results could be due to random chance, rather than a definitive effect of treatment.
Both trials of astegolimab involved ‘all-comers’ patient population
To further test the therapy, the ALIENTO and ARNASA studies each enrolled about 1,300 adults with COPD. To be eligible, participants needed to have experienced at least two moderate or severe exacerbations in the year prior to entering the trial.
Genentech noted that the studies included a broad population, with both current and former smokers, and enrolled participants regardless of eosinophils counts. Eosinophils are a type of immune cell sometimes elevated in COPD and known to contribute to the disease.
“This was the first set of studies in an ‘all-comers’ COPD population,” Garraway said. The release noted that the participants “have a history of frequent exacerbations.”
In both trials, the participants were randomly divided into three groups. One group received astegolimab injections every other week, and a second group received injections with a placebo on the same schedule. The third group received alternating injections of astegolimab and placebo — so, in effect, those patients were treated with astegolimab every four weeks. All participants continued to receive standard-of-care maintenance therapies.
Therapy met goal in 1 trial, failed in the other
The main goal in both studies was to assess rates of moderate or severe COPD exacerbations after a year.
Top-line results from ALIENTO showed that every-other-week astegolimab treatment was associated with a 15.4% lower yearly exacerbation rate relative to the placebo, and this difference was statistically significant.
In ARNASA, patients’ yearly exacerbation rate was 14.5% lower with astegolimab, but this difference failed to reach statistical significance.
Genentech noted that overall exacerbation rates were lower than expected in both clinical trials, and that the safety profile of astegolimab was consistent with data from prior studies.
Also, the results “were generally consistent across secondary endpoints [goals] in both studies,” the release stated. These enpoints included time to first moderate or severe COPD exacerbation, as well as changes in lung function, symptoms, and health-related quality of life.
Participants who completed the ALIENTO and ARNASA studies had the option to enter a long-term extension study (NCT05878769) in which all are being treated with astegolimab every other week over a longer period.
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