Phase 3 trial testing benralizumab in COPD patients misses main goal
Developer AstraZeneca will pivot its focus to other therapies
A Phase 3 clinical trial testing AstraZeneca’s injection therapy benralizumab as a potential treatment for chronic obstructive pulmonary disease (COPD) has failed to meet its main goal of showing the therapy’s superiority over a placebo in terms of the ability to reduce the rate of moderate or severe COPD exacerbations.
Following the trial’s negative results, the company stated it will pivot its focus to developing other potential COPD therapies.
“COPD, which remains a leading cause of death worldwide, is a complex, heterogeneous disease, and we continue to advance other promising approaches in our pipeline to address the unmet needs of patients,” Sharon Barr, executive vice president of biopharmaceuticals research and development at AstraZeneca, said in a company press release.
Benralizumab has consistently failed to show a benefit in COPD
Benralizumab is an antibody-based therapy designed to block the activity of the interleukin-5 signaling pathway, which promotes the survival and inflammatory activity of immune cells called eosinophils. These cells are thought to help drive lung inflammation in COPD, so it was hoped the therapy might reduce disease exacerbations where lung inflammation worsens. The medication is given by an under-the-skin injection, or subcutaneously.
AstraZeneca sponsored a Phase 3 clinical trial called RESOLUTE (NCT04053634), which enrolled nearly 700 people with moderate to very severe COPD who had high eosinophil levels and a history of frequent exacerbations, or episodes of disease worsening.
Participants were randomly assigned to receive either benralizumab or a placebo, with the main goal of seeing if the therapy could lower the rate of moderate or severe COPD exacerbation after about a year. Injections were given monthly for the first three doses and every other month after that.
AstraZeneca has now announced that the trial failed to meet its main goal. The company said exacerbation rates were lower in patients given benralizumab than in those treated with a placebo. However, the difference was not statistically significant, meaning it’s mathematically plausible that the difference could just be due to random chance. The therapy’s safety and tolerability profile in RESOLUTE was consistent with its known safety profile.
This isn’t the first trial testing benralizumab in COPD patients that has missed its goal. In the late 2010s, two other Phase 3 trials — GALATHEA (NCT02138916) and TERRANOVA (NCT02155660) — also failed to demonstrate benralizumab’s ability to reduce COPD exacerbation rates.
Although benralizumab has consistently failed to show a benefit in COPD, it has shown benefits in other eosinophil-driven disorders. The therapy is widely approved under the brand name Fasenra as a treatment for severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis, a rare form of ANCA-associated vasculitis. It is also under regulatory review for hypereosinophilic syndrome.
“With its well-established ability to target and eliminate eosinophils, Fasenra has helped transform treatment of severe asthma, and more recently has demonstrated a significant effect in eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome,” Barr said.
AstraZeneca also stated it will further examine the trial results, which will be shared with the scientific community in the future.
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