Benralizumab Achieves Positive Outcomes in Eosinophilic Exacerbations in Asthma, COPD

Author(s):

Gillian McGovern, Assistant Editor

Key Takeaways

Benralizumab demonstrated superior efficacy over standard care in reducing treatment failures and improving symptoms in asthma and COPD exacerbations.
The ABRA trial involved 158 patients, showing significant reduction in treatment failures with benralizumab compared to prednisolone alone.
Benralizumab was well-tolerated, with no fatal adverse events, indicating its safety for patients with asthma and COPD.
The study highlights the potential for targeted therapy in managing high-risk asthma and COPD patients, suggesting a shift in treatment approaches.

Compared prednisolone alone, benralizumab with and without prednisolone resulted in fewer treatment failures and stronger VAS scores.

Image credit: Sebastian Kaulitzki | stock.adobe.com

Benralizumab (Fasenra; AstraZeneca, BioWa Inc.) can be used for a treatment for acute eosinophilic endotypes of asthma and chronic obstructive pulmonary disease (COPD) exacerbations, according to results from the BenRAlizumab trial (ABRA; NCT04098718) published in The Lancet Respiratory Medicine. The investigators noted that these results are significant, because benralizumab was more effective than standard of care treatments, potentially solidifying itself as a new method of treating exacerbations.¹

Benralizumab is a humanized monoclonal antibody that targets interleukin (IL)-5 receptor-α and can be used to treat asthma and COPD. For ABRA, a multicenter, double-blind, double-dummy, active placebo-controlled phase 2 trial (NCT04098718), the investigators assessed the efficacy of benralizumab with or without prednisolone (Orapred; BioMarin Pharmaceutical, Alliant Pharmaceuticals) will improve outcomes in patients with a diagnosis of asthma or COPD. A total of 158 patients were enrolled and included in the final analysis, all of whom had at least 1 exacerbation within the past 12 months that required treatment with oral or intravenous corticosteroids and/or prior evidence (within 2 years) of eosinophilic inflammation.^1,2

Patients were randomly assigned to receive acute treatment with the following: 30 mg of prednisolone once per day for 5 days and 100 mg of benralizumab injected subcutaneously once (n = 52; BENRA plus PRED group); placebo tablets administered once per day for 5 days and 100 mg of benralizumab injected subcutaneously once (n = 53; BENRA group); or 30 mg of prednisolone once per day for 5 days and placebo injection subcutaneously once (n = 53; PRED group). The trial’s co-primary outcomes were proportion of treatment failures over a 90-day period and total visual analogue scale (VAS) symptoms at day 28 in the 2 benralizumab groups compared with the prednisolone alone group.^1,2

According to the investigators, most of the enrolled patients were women (n = 86; 54%) with a mean age of about 57 years (range: 18-84 years). At the 90-day point, treatment failures were observed in approximately 74% (n = 39) of patients in the PRED group compared with 45% (n = 47) in the 2 benralizumab groups (OR 0.26, 95% CI 0.13–0.56; p = .0005). Additionally, the total Visual Analogue Scale (VAS) mean difference had also favored the benralizumab groups, with an observed difference of 49 mm (95% CI 14–84; p = .0065).¹

About the Trial

Trial Name: Acute Exacerbations Treated With BenRAlizumab (The ABRA Study) (ABRA)

ClinicalTrials.gov ID: NCT04098718

Sponsor: University of Oxford

Completion Date (Estimated): November 19, 2024

“The big advance in the ABRA study is the finding that targeted therapy works in asthma and COPD attacks. Instead of giving everyone the same treatment, we found targeting the highest risk patients with very targeted treatment, with the right level of inflammation was much better than guessing what treatment they needed,” Mona Bafadhel, MB ChB, PhD, professor and chair of respiratory medicine at King’s College London, said in a news release. “We hope these pivotal studies will change how asthma and COPD exacerbations are treated for the future, ultimately improving the health for over a billion people living with asthma and COPD across the world.”³

Further, the investigators noted there were no fatal adverse events present in the benralizumab groups, indicating the agent was well-tolerated by patients. Some instances of hyperglycemia and sinusitis or sinus infection were observed, but the investigators found that these were related to prednisolone.¹

“Our study shows massive promise for asthma and COPD treatment. COPD is the third leading cause of death worldwide but treatment for the condition is stuck in the 20th century. We need to provide these patients with life-saving options before their time runs out,” Sanjay Ramakrishnan, PhD, clinical senior lecturer at the University of Western Australia, said in the news release.³

REFERENCES

1. Ramakrishnan S, Russell REK, Mahmood HR, et al. Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial. Lancet Respir Med. 2024. doi:10.1016/S2213-2600(24)00299-6

2. Top of FormAcute Exacerbations Treated With BenRAlizumab (The ABRA Study) (ABRA). ClinicalTrials.gov identifier: NCT04098718. Updated January 23, 2024. Accessed December 6, 2024. https://clinicaltrials.gov/study/NCT04098718

3. SciTechDaily. “Game-Changing” New Treatment for Asthma Could Save Millions From Fatal Lung Attacks. News release. December 3, 2024. Accessed December 6, 2024. https://scitechdaily.com/game-changing-new-treatment-for-asthma-could-save-millions-from-fatal-lung-attacks/