Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, debilitating form of vasculitis which results in reduced blood flow and —subsequently — potential organ damage in patients. The disease affects 10 in a million per year and currently has no cure.1
Although there are therapies available for this condition, many patients don’t sufficiently respond to treatment, while many are strongly impacted by side effects from chronic oral corticosteroid (OCS) usage; a common therapeutic strategy for EGPA.
To combat this significant unmet need, AstraZeneca has run trials to determine if Fasenra (benralizumab), the company’s proprietary therapeutic approved for the treatment of severe eosinophilic asthma (SEA), is capable of treating EGPA, with the recent MANDARA trial determining the non-inferiority of Fasenra in comparison to the one currently approved drug for EGPA, mepolizumab.2
Annabel Kartal-Allen caught up with Dr Michael Wechsler, Professor of Medicine, Director of The Asthma Institute at National Jewish Health and International Coordinating Investigator of the MANDARA trial to find out more.
The trial
Dr Wechsler elaborates on the successes of the trial: “MANDARA was the first head to head trial of biologics in patients with EGPA and was designed to test for the ability of Fasenra to match the efficacy of mepolizumab. Fasenra ended up meeting the primary endpoint, which was non-inferiority, while also demonstrating that remission is an achievable goal for EGPA patients.”
treatment with benralizumab led to a more substantial reduction in blood eosinophil counts compared to mepolizumab
As well as matching the efficacy of the current treatment available on the market, Fasenra outperformed mepolizumab when discussing eosinophilic depletion, Dr Wechsler explains: “Additionally, eosinophil-depletion analysis revealed that treatment with benralizumab led to a more substantial reduction in blood eosinophil counts compared to mepolizumab.”
Giving patients options
The oversubscription of oral corticosteroids (OCS) is a significant problem in the EGPA patient population, with many serious side effects being implicated in chronic usage. Therefore, available solutions for patients experiencing these symptoms is a significant area of unmet need in patient care.
Fasenra’s potential ability to alleviate the stress patients experience could improve quality of life, Dr Wechsler explains: “Benralizumab enabled a higher proportion of patients to taper off OCS in the study, with a higher proportion of those allocated to the benralizumab arm being able to successfully discontinue OCS. This could allow patients to break the cycle of chronic usage and mediate the negative impacts associated with this.”
As well as some patients not being able to benefit from available treatments due to reduced efficacy, some are not even able to access medicines in the first place: “Only one third of eligible patients are currently receiving an approved treatment, while patients treated with high-dose OCS often experience serious and lasting side-effects, as well as recurrent relapses when attempting to taper off.”
“ The inclusion of benralizumab in the treatment pipeline could alleviate some of the impacts of this disease, and give patients a break from OCSs.”
Expanding Fasenra’s capability
With Fasenra already being approved as a maintenance therapy for severe eosinophilic asthma (SEA) in the US and the European Union, the MANDARA trial has further expanded the known benefits of this drug.
To expand on the growing demonstrable abilities of Fasenra to treat patients with eosinophilic disorders, further initiatives by AstraZeneca have been placed in the pipeline to determine the efficacy of this drug in a range of diseases such as chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome3-5.
References
1 https://www.brighamandwomens.org/lung-center/diseases-and-conditions/eosinophilic-granulomatosis-with-polyangiitis#:~:text=A%20rare%20systemic%20vasculitis%20affecting,vessels%20in%20people%20with%20asthma.
2 Clinicaltrials.gov. Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. (MANDARA). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04157348. [Last accessed: September 2023].
3 Clinicaltrials.gov. Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE). Available from: https://clinicaltrials.gov/ct2/show/NCT04053634. [Last accessed: September 2023].
4 Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID). Available at: https://clinicaltrials.gov/ct2/show/NCT04157335. [Last accessed: September 2023].
5 Clinicaltrials.gov. A Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Patients With Hypereosinophilic Syndrome (HES) (NATRON). Available from: https://clinicaltrials.gov/ct2/show/NCT04191304. [Last accessed: September 2023].