Frequent or chronic use of oral corticosteroids can lead to serious adverse effects in patients with asthma, including weight gain, diabetes, immunosuppression, and adrenal insufficiency.
A new trial of benralizumab (Fasenra, AstraZeneca) in oral corticosteroid (OCS)-dependent patients with asthma found that 62% of patients who received benralizumab stopped OCS use.
Severe asthma can be a severely debilitating condition affecting approximately 34 million people globally, with more than one-third of these patients using chronic or intermittent OCS in addition to other therapies to control their symptoms and exacerbations. Despite this common reliance on OCS, frequent or chronic use of these drugs can lead to serious adverse effects, including weight gain, diabetes, immunosuppression, and adrenal insufficiency.
The PONENTE study is a multicenter, open-label, single-arm, phase 3 trial evaluating the efficacy and safety of reducing daily OCS use after initiation of a 30 mg dose of benralizumab, which is administered subcutaneously in adults with severe eosinophilic asthma. Participants had been on a maintenance OCS dose of 5 mg or more of prednisone for at least 3 months. The treatment period consisted of a 4-week induction phase with no OCS adjustments, a variable OCS tapering phase, and an ongoing 24- to 34-week maintenance phase.
According to a press release, 62% of patients achieved complete elimination of daily OCS use, which was the first primary endpoint. On the second primary endpoint, 81% of patients achieved complete elimination or were able to reduce their daily OCS dose to 5 mg or less when adrenal insufficiency made further reduction impossible. Both primary endpoints were sustained for at least 4 weeks while maintaining asthma control, according to the study.
“These exciting results demonstrate Fasenra’s impact in eliminating or reducing oral corticosteroid use,” said principal investigator Andrew Menzies-Gow, MD, in a press release. “The reductions achieved with the personalized oral corticosteroid tapering schedule are particularly important because adrenal insufficiency can be a barrier to safe and meaningful oral corticosteroid reduction. These data should inform severe asthma treatment guidelines and strengthen physicians’ confidence to more safely eliminate chronic oral corticosteroid use in their patients.”
These findings expand on OCS-sparing data from the earlier ZONDA phase 3 trial by using a faster steroid tapering schedule in patients who did not experience adrenal insufficiency to reduce OCS use from higher doses. The PONENTE trial also has a longer maintenance phase, which shows more durable OCS reduction and asthma control than was seen in other published trials.
Benralizumab is currently approved as an add-on maintenance treatment for severe eosinophilic asthma and is approved for self-administration. According to the press release, it is also being evaluated in 8 eosinophil-driven diseases beyond severe asthma.
“Around 13.5 million people worldwide with severe asthma currently rely on oral corticosteroids to control exacerbations and prevent hospitalizations,” said Mene Pangalos, executive vice president of Biopharmaceuticals research and development, in a press release. “However, over-reliance on oral corticosteroids can also cause significant health risks for patients, as well as additional strain on health systems. These data further support Fasenra’s clinical profile in eliminating oral corticosteroid use across a broader population of severe asthma patients.”
Fasenra eliminated oral corticosteroid use in a majority of OCS-dependent patients with asthma in PONENTE Phase IIIb trial [news release]. AstraZeneca; October 29, 2020. https://www.astrazeneca.com/media-centre/press-releases/2020/fasenra-eliminated-oral-corticosteroid-use-in-a-majority-of-ocs-dependent-patients-with-asthma-in-ponente-phase-iiib-trial.html. Accessed November 6, 2020.