Benralizumab for ANCA-associated vasculitis
Last updated Sept. 12, 2024, by Marisa Wexler, MS
Fact-checked by Marta Figueiredo, PhD
What is benralizumab for ANCA-associated vasculitis?
Benralizumab is an under-the-skin, or subcutaneous, injectable therapy being explored as a potential treatment for eosinophilic granulomatosis with polyangiitis (EGPA), a rare form of ANCA-associated vasculitis (AAV).
The therapy was developed by AstraZeneca and its global biologics research and development arm MedImmune. It’s already approved under the name Fasenra in North America, Europe, and other regions for treating severe eosinophilic asthma, a rare type of asthma that’s associated with high numbers of eosinophils, a type of immune cell.
Given that asthma and excessive eosinophils are hallmarks of EGPA, benralizumab is being developed as an add-on to EGPA standard care with glucocorticoids to promote and maintain disease remission. The therapy is also expected to help reduce the need for glucocorticoids, whose long-term use is linked to serious side effects.
Therapy snapshot
Treatment name: | Benralizumab |
Administration: | Being tested in EGPA as a subcutaneous injection |
Clinical testing: | Completed a Phase 3 trial in EGPA patients |
How does benralizumab work in ANCA-associated vasculitis?
Like other types of ANCA-associated vasculitis, EGPA is an autoimmune disease marked by damaging inflammation in small blood vessels that can affect the function of several organs and tissues.
In EGPA, the rarest AAV type, small clumps of eosinophils build up in small blood vessels and nearly all patients have very high counts of eosinophils at some point in their disease course. Eosinophils normally defend the body against parasites, bacteria, and viruses, but can also cause damage as part of the inflammatory responses triggered by allergies.
The disease causes symptoms that most often affect the respiratory tract, leading to asthma in more than 90% of cases, and the gastrointestinal tract.
The mainstay treatment for EGPA consists of anti-inflammatory oral medications called glucocorticoids. High doses of and/or long-term treatment with glucocorticoids can result in serious side effects such as high blood pressure, diabetes, weight gain, and sleep and mental health problems, however.
Benralizumab, formerly MEDI-563, is an antibody-based therapy designed to bind and prevent the activation of IL-5 receptor alpha (IL-5R-alpha), a protein activated by IL-5 and found almost exclusively on the surface of eosinophils. IL-5/IL-5R-alpha signaling is essential for the growth, activation, and survival of eosinophils.
Benralizumab blocks this signaling and also causes the death of eosinophils by boosting the binding of other immune cells to benralizumab-covered eosinophils and their precursors, promoting their death.
As such, the therapy is expected to limit disease-driving inflammation, promote disease remission, and reduce risk of relapse in people with EGPA.
Benralizumab’s mechanism of action is similar to that of GSK’s Nucala (mepolizumab), which is approved for EGPA as an add-on to glucocorticoids. Nucala, given as three separate subcutaneous injections every four weeks, is an antibody-based therapy that promotes eosinophil death only indirectly by targeting IL-5.
How will benralizumab be administered in ANCA-associated vasculitis?
Benralizumab is available as a single-dose prefilled syringe containing either 10 mg or 30 mg of the active ingredient. A 30 mg single-dose autoinjector, intended for patients and caregivers to administer after appropriate training, is also available.
In EGPA clinical trials, the medication was given as a single subcutaneous injection of 30 mg, once every four weeks.
Benralizumab in ANCA-associated vasculitis clinical trials
AstraZeneca launched a global head-to-head Phase 3 clinical trial, called MANDARA (NCT04157348), to evaluate benralizumab’s safety and effectiveness against Nucala in 140 adults with hard to treat EGPA.
All had relapsed after three months, but less than two years, before enrolling; had failed to achieve disease remission following standard induction regimen; or had symptom recurrence upon oral glucocorticoid tapering at doses of at least 7.5 mg per day.
The participants, who all were receiving stable doses of oral glucocorticoids with or without stable immunosuppressive treatment, were randomly assigned to benralizumab or Nucala for about a year.
Benralizumab was given as one 30 mg injection every four weeks and Nucala as three 100 mg injections every four weeks. Patients could continue their standard-of-care treatment.
The study’s main goal was to determine if benralizumab was at least as effective as Nucala at inducing disease remission at both weeks 36 and 48. This was assessed through the proportion of patients who achieved remission, defined as a Birmingham Vasculitis Activity Score of 0 (no symptoms) while taking 4 mg/day or less of oral glucocorticoids.
Secondary goals included remission duration, time to first relapse, relapse rates, changes in disease severity and activity, and the proportion of patients able to reduce their corticosteroid dose. Other measures included side effects and the number of hospitalizations and emergency care visits related to EGPA.
Top-line results, announced in 2023, showed remission rates were comparable between treatment groups: 59% with benralizumab and 56% with Nucala.
Secondary measures also supported that benralizumab was not inferior to Nucala. Specifically, no significant differences were seen regarding remission duration, the proportion of patients in remission within six months who stayed in remission to a year (42% vs. 36%), and relapse rates (30% in both groups).
In the last four weeks of treatment, a higher proportion of benralizumab-treated patients reduced their oral glucocorticoid dose by at least 50% (86% vs. 74%) and were able to fully taper off these medications (41% vs. 26%).
Moreover, benralizumab treatment was associated with greater reductions in blood eosinophil counts, starting as early as the first week and sustained through a year of treatment.
Safety data from both therapies were comparable.
Those who completed the one-year treatment could choose to move into the trial’s open-label extension phase, where all received benralizumab for a year.
Common side effects of benralizumab
In the Phase 3 MANDARA trial, rates of adverse events were generally similar between benralizumab and Nucala treatment groups, with the most common adverse events being COVID-19 infection, headache, and joint pain.
There have been no reports of benralizumab side effects in EGPA patients to date, but in people with severe eosinophilic asthma, the most commonly reported side effects are headache and symptoms of common cold.
Note: ANCA Vasculitis News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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