AstraZeneca at ATS’24: Andrew Menzies-Gow from AstraZeneca in a Stimulating Conversation with PharmaShots

Shots:

AstraZeneca presented 59 abstracts, including 12 late-breaking posters at the American Thoracic Society, focussing on the unmet needs in COPD, EGPA, and other chronic respiratory diseases

Today, at PharmaShots, we have Andrew Menzies-Gow, sharing insights from the MANDARA study that evaluated Fasenra (benralizumab) for EGPA, a rare debilitating condition

Andrew stresses reducing the use of oral glucocorticoid (OGC) in patients with EGPA

Saurabh: Can you elaborate on the significance of reducing oral glucocorticoid (OGC) use in patients with eosinophilic granulomatosis with polyangiitis (EGPA)?

Andrew: The ability to taper or potentially eliminate OCS use is a significant step for patients. Patients treated with high-dose OCS often experience serious and lasting side-effects, as well as recurrent relapses when attempting to taper off.  

Saurabh: EGPA is a rare disease. How do these findings from the MANDARA study contribute to the overall understanding and treatment of EGPA?

Andrew: There is a high unmet medical need in EGPA as there are limited treatment options and not all patients respond to currently available treatments. Having another option that could help patients achieve remission and reduce chronic OCS usage, in a single injection every four weeks, could alleviate some of the impact of this debilitating disease. 

There is only one approved treatment for EGPA: the comparator in the MANDARA trial.

Only one third of eligible patients receive an approved treatment (in the top seven countries). Patients are often treated with high-dose OCS, which cause serious and lasting side-effects, and often suffer recurrent relapses when attempting to taper off OCS.

MANDARA was the first trial to demonstrate that more than half of patients with EGPA achieved remission with eosinophil-targeted biologics. Benralizumab also enabled patients to taper off OCS while preventing major relapses.

Saurabh: Could you help us understand if any other effective treatments are available to reduce OGC dependence while controlling EGPA?

Andrew: There is only one other approved biologic treatment for EGPA, the comparator in the MANDARA trial.

Saurabh: While both medications achieved similar relapse rates, were there any other key differences observed between benralizumab and mepolizumab in the study?

Andrew: MANDARA was designed as a non-inferiority trial and was not powered to show superiority between Fasenra and mepolizumab. Fasenra met the primary endpoint, demonstrating remission rates that were non-inferior to mepolizumab. There were some differences in outcomes between benralizumab and mepolizumab. Remission: adjusted rate of remission was 59% for benralizumab-treated patients at weeks 36 and 48, compared with 56% for mepolizumab (difference in rates: 3%; 95% CI:, –13,18).

OCS tapering: a higher number of benralizumab-treated patients were able to fully taper off OCS during weeks 48 through 52, 41% in the benralizumab arm vs. 26% in the comparator arm (difference: 16%; 95% CI: 1 to31).

Eosinophil-depletion: treatment with benralizumab was associated with a greater reduction of blood eosinophil counts from week 1 compared to mepolizumab and maintained at all timepoints. At week 1, mean blood eosinophil count ratio to baseline was 0.15 vs. 0.39 respectively (adjusted geometric mean ratio: 0.38; 95% CI: 0.29, 0.49) and 0.10 vs. 0.26 at week 52 (adjusted geometric mean ratio: 0.36; 95% CI: 0.27, 0.49).

Saurabh: Can you delve deeper into the mechanism by which benralizumab might be more effective in reducing OGC use compared to mepolizumab?

Andrew: Benralizumab is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils. We know that elevated eosinophils play a central role in EGPA disease pathophysiology.

Saurabh: How accessible are these medications for patients with EGPA, and are there any specific considerations for their use?

Andrew: Fasenra is not yet approved for EGPA. We are currently seeking approval for the EGPA indication in the EU, US and Japan.

Saurabh: With these study results, how optimistic are you able the future of EGPA treatment?

Andrew: We are very optimistic about the future of treatments for patients with EGPA. The MANDARA trial demonstrated that benralizumab could be an additional treatment option available to patients.

Image Source: Canva

About the Author:

Andrew Mezies-Gow

Andrew Menzies-Gow is the Global Medical Head for Respiratory Biologics at AstraZeneca. Prior to joining the company in January 2023 Andrew was the clinical and research lead for the adult severe asthma service and Director of the Lung Division at the Royal Brompton & Harefield Hospitals, London, UK. Andrew was a Professor of Practice (Respiratory Medicine) at Imperial College, London, UK, where his research interests focussed on novel therapies for severe asthma and was the National Clinical Director for Respiratory Disease at NHS England.