Republished from Astrazeneca Canada.

New indication supported by the MANDARA trial, which showed 58% of patients achieved remission and 41% of patients fully stopped taking oral corticosteroids

Mississauga, ON, July 21, 2025 – Health Canada has granted a Notice of Compliance (NOC) for Fasenra® (benralizumab injection) as an add-on treatment of adult patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA).¹ EGPA is a rare, immune-mediated vasculitis that can result in damage to multiple organs, and without treatment, may be fatal.^2,3

“EGPA can have a devastating impact on a person’s quality of life with debilitating symptoms including new onset asthma, significant neuropathy, pulmonary infiltrates, extreme fatigue, weight loss, pain, rashes, organ damage, abnormal levels of eosinophils, and in some cases even death,” says Jon Stewart, President, Vasculitis Foundation of Canada. “The approval of Fasenra in Canada for people living with EGPA provides a valuable new treatment option to help those living with this rare disease, and life-threatening form of vasculitis.”

“Living with asthma can be incredibly challenging, and the risk of developing EGPA is 34 times higher for these individuals, adding a significant burden to their daily lives,” says Jeffrey Beach, President & CEO of Asthma Canada. “Today’s announcement provides a welcome new option for people in Canada living with EGPA.”

This approval was based on results from the Phase III MANDARA trial, published in The New England Journal of Medicine.⁴ The trial compared the efficacy and safety of Fasenra to the only approved EGPA treatment, mepolizumab, in patients with relapsing or refractory EGPA.^4-6 MANDARA was the first head-to-head non-inferiority trial of biologics in patients with EGPA.^5-6 Patients were randomized to receive either a single 30 mg subcutaneous injection of Fasenra, or three separate 100 mg subcutaneous injections of mepolizumab every four weeks. ^4,5 In the trial, 58% of Fasenra-treated patients achieved remission, which was comparable to mepolizumab-treated patients.⁴ Data also showed 41% of Fasenra-treated patients fully tapered off oral corticosteroids (OCS) (vs. 27% in the comparator arm (difference: 16%; 95% CI: 1,31)).⁴ The safety and tolerability profile for Fasenra in the MANDARA trial was consistent with the known profile of the medicine.⁴

“Treatment options for patients with EGPA have historically been limited, with many relying on the long-term use of oral corticosteroids, which cause serious and lasting side effects,” says Dr. Krystelle Godbout, Respirologist, Chief of the IUCPQ severe asthma clinic. “The approval of Fasenra offers a safe and effective option for treatment of this rare disease with evidence suggesting that achieving remission is possible while significantly reducing the average daily oral corticosteroid dose.”

Approximately half of patients with EGPA have adult-onset severe eosinophilic asthma (SEA) and often have sinus and nasal symptoms.^3,7,8 Fasenra is only the second biologic approved to treat this disease.

Fasenra

Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

Eosinophilic granulomatosis with polyangiitis

EGPA, formerly known as Churg-Strauss Syndrome, is a rare, immune-mediated inflammatory disease that is caused by inflammation of small to medium-sized blood vessels.^2,3 It is estimated that 118,000 people throughout the world live with EGPA and approximately 630 patients in Canada.⁹ EGPA can result in damage to multiple organs, including lungs, upper airway, skin, heart, gastrointestinal tract and nerves.³ The most common symptoms and signs include extreme fatigue, weight loss, muscle and joint pain, rashes, nerve pain, sinus and nasal symptoms, and shortness of breath.^3,10 Without treatment, the disease may be fatal.^3,11 Almost half (47%) of patients do not achieve remission with current treatments.¹⁰

There are limited treatment options for EGPA. Patients are often treated with chronic high-dose OCS and experience recurrent relapses when attempting to taper off OCS.^10,11

For more information on EGPA please visit www.vasculitis.ca.

MANDARA

MANDARA was a Phase III, randomized, double-blinded, active-controlled trial, which compared the efficacy and safety of benralizumab to mepolizumab in adult patients with relapsing or refractory EGPA.⁵ In the trial, 140 patients, including 19 in Canada, were randomized 1:1 to receive either a single 30 mg subcutaneous injection of benralizumab or three separate 100 mg subcutaneous injections of the active comparator every four weeks.⁴

The primary endpoint was the proportion of patients who were in remission at both weeks 36 and 48.⁵ Remission is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4 mg/day.⁵ A secondary endpoint was the proportion of patients who were able to fully taper off OCS at weeks 48 through 52.⁵ The primary statistical analysis was to demonstrate non-inferiority of benralizumab versus mepolizumab based on the primary endpoint.⁴ Key secondary endpoints included the accrued duration of remission, time to first relapse, oral glucocorticoid use, eosinophil count and, safety. Study limitations include the small sample size due to the low prevalence of EGPA and secondary endpoints that were not multiplicity-corrected, which limited their interpretation.⁴

AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a focus on the discovery, development, and commercialization of medicines that transform lives, with a core scientific focus in the areas of Cardiovascular, Renal and Metabolic (CVRM) disease; Oncology; Rare Disease; Respiratory & Immunology; and Vaccine & Immune Therapies. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide.

The company employs more than 2,400 people across Canada, and recently announced a major expansion of its Mississauga-based Research & Development Hub and the creation of a new Alexion Development Hub focused on rare diseases. The company is one of Canada’s leading R&D contributors, investing $230M in Canadian R&D in 2023. To learn more visit www.astrazeneca.ca.

Contact:

Corporate Communications: corporatecommunications@astrazeneca.com

References:

1. 1. AstraZeneca Canada Inc., FASENRA^® (benralizumab injection), Product Monograph. July 2025.
   2. Furuta S, et al. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68:430-436.
   3. Vasculitis Foundation Canada. Eosinophilic Granulomatosis with Polyangiitis (EGPA). Available at: https://vasculitis.ca/wp-content/uploads/2021/06/EGPAInfoSheet.pdf . [Last accessed: January 2025]
   4. Wechsler ME, et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024;390(10):911-921.
   5. Clinicaltrials.gov. Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. (MANDARA). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04157348. [Last accessed: January 2025].
   6. Health Canada. Drug Product Database. https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=98296. Last accessed December 2024.
   7. Cottin V, et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). Eur Respir J. 2016;48:1429-1441.
   8. Heaney L et al. Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort. Chest. 2021 Sep;160(3):814-830.
   9. AstraZeneca data on file. 2024. REF- 244520.
   10. Baldini C, et al. Clinical Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis Clin N Am. 2010;36:527–543.
   11. Bell CF, et al. Burden of illness and costs associated with eosinophilic granulomatosis with polyangiitis: evidence from a managed care database in the United States. J Manag Care Spec Pharm. 2021;27(9):1249-1259.