Phase 3 Trial of Benralizumab for COPD Misses Primary Endpoint

Sean Bohen, MD, PhD

AstraZeneca and MedImmune, its global biologics research and development arm, announced negative topline results from a phase 3 trial of benralizumab for treating chronic obstructive pulmonary disease.

Benralizumab is a monoclonal antibody that enlists natural killer cells to cause a rapid and nearly complete depletion of eosinophils.

In the GALATHEA phase 3 trial, benralizumab (Fasenra) did not achieve its primary endpoint of a statistically significant reduction of exacerbations in patients with chronic obstructive pulmonary disease (COPD) with a history of exacerbations across a range of baseline blood eosinophils.

The company reported that COPD affects an estimated 384 million people worldwide and is predicted to be the third-leading cause of death by 2020. Additionally, the AstraZeneca statement noted that 30-40% of moderate to severe COPD patients on triple inhaled therapy have uncontrolled symptoms and continue to face exacerbations.

A second phase 3 trial of benralizumab, TERRANOVA, is ongoing and the company expects results later this quarter. Both GALATHEA and TERRANOVA are randomized, double-blinded, 56-week placebo-controlled, multi-center trials.

Each study aims to measure the safety and efficacy of benralizumab as an addition to dual or triple inhaled therapy compared to placebo in patients with moderate to very severe COPD, who have a history of exacerbations.

“COPD is a debilitating disease with significant unmet need among patients whose disease remains uncontrolled despite treatment with existing inhaled therapies. We will now await the results of TERRANOVA and a full evaluation of both trials to determine next steps for Fasenra in COPD,” said Sean Bohen, MD, PhD, Executive Vice President, Global Medicines Development and Chief Medical Officer of AstraZeneca.

In 2017, benralizumab received US Food and Drug Administration (FDA) approval for treatment of severe eosinophilic asthma following the successful WINDWARD program, a combination of 6 phase 3 trials, including 2 pivotal trials SIROCCO and CALIMA.

The SIROCCO trial found that benralizumab reduced the annual rate of exacerbations by up to 51% after 48 weeks of treatment. CALIMA’s results showed at 36% decline after 56 weeks.

"The worldwide prevalence of asthma continues to increase and is projected to reach more than 400 million by 2020, representing a growing unmet need for the treatment of patients with uncontrolled disease," the lead author of the SIROCCO paper, Eugene R. Bleecker, MD, and his colleagues wrote.

Benralizumab was AstraZeneca’s first respiratory biologic and is currently approved for treating severe eosinophilic asthma in the US, EU, Japan, Canada, and Australia.

The negative results of the GALATHEA trial do not impact the FDA-approved indication in severe eosinophilic asthma.