Fasenra approved in the EU for eosinophilic granulomatosis with polyangiitis

New indication supported by the MANDARA trial, which showed nearly 60% of patients achieved remission and 41% of patients fully stopped taking oral corticosteroids

AstraZeneca’s Fasenra (benralizumab) has been approved in the European Union (EU) as an add-on treatment for adult patients with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA). EGPA is a rare, immune-mediated vasculitis that can result in damage to multiple organs, and without treatment, can be fatal.^1,2

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on positive results from the MANDARA Phase III trial, published in The New England Journal of Medicine.³ MANDARA was the first head-to-head non-inferiority trial of biologics in patients with EGPA.^4-6 Patients were randomised to receive either a single 30 mg subcutaneous injection of Fasenra, or three separate 100 mg subcutaneous injections of mepolizumab every four weeks. ^3,4   

In the trial, nearly 60% of Fasenra-treated patients achieved remission, which was comparable to mepolizumab-treated patients.³ Data also showed 41% of Fasenra-treated patients fully tapered off oral corticosteroids (OCS) (vs. 26% in the comparator arm (difference: 16%; 95% CI: 1,31)).³

Bernhard Hellmich, Chair of the Department of Internal Medicine, Rheumatology, and Immunology at the Medius Klinik Kirchheim, Teaching Hospital of the University of Tübingen in Germany, Co-Director of the Vasculitis Center Tübingen-Kirchhei, and MANDARA Principal Investigator said: “People living with EGPA suffer debilitating symptoms, organ damage and even death. Today’s approval provides an important treatment option for people living with EGPA in the EU. By directly targeting and removing eosinophilic inflammation with benralizumab, I hope that we will see more patients achieve remission as well as a reduction in the reliance on oral corticosteroids, which can cause serious and long-term side effects.”   

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca said: “We remain committed to helping patients with some of the hardest-to-treat diseases. Today’s approval of Fasenra, with its convenient, single-monthly injection is a positive step forward for patients with EGPA. Fasenra has been a well-established treatment for many years in thousands of people with severe eosinophilic asthma and we are pleased to now offer a much-needed treatment option for those living with EGPA in Europe.”   

The safety and tolerability profile for Fasenra in the MANDARA trial was consistent with the known profile of the medicine.³     

Approximately half of patients with EGPA have adult-onset severe eosinophilic asthma (SEA) and often have sinus and nasal symptoms.^2,7,8 Fasenra is only the second biologic approved to treat this disease.⁵     

Fasenra is currently approved as an add-on maintenance treatment for SEA in more than 80 countries, including the US, Japan, EU and China.^9-12 It is also approved in children and adolescents ages 6 and above in the US and Japan. Fasenra was approved for EGPA in the US in September.¹³

References

1. Furuta S, et al. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68:430-436. 

2. American Partnership for Eosinophilic Disorders. Eosinophilic Granulomatosis with Polyangiitis (EGPA). Available at: https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/. [Last accessed: October 2024].

3. Wechsler ME, et al. Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2024;390(10):911-921.

4. Clinicaltrials.gov. Efficacy and Safety of Benralizumab in EGPA Compared to Mepolizumab. (MANDARA). Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04157348. [Last accessed: October 2024].

5. Mepolizumab US prescribing information. Available from: https://www.fda.gov/files/drugs/published/125526-Mepolizumab-Clinical-PREA.pdf [Last accessed: October 2024].

6. AstraZeneca plc. MANDARA Phase III data published in New England Journal of Medicine show remission is an achievable goal in eosinophilic granulomatosis with polyangiitis (EGPA) with Fasenra. Available at: https://www.astrazeneca.com/media-centre/medical-releases/mandara-phase-iii-data-published-new-england-journal-medicine-show-remission-achievable-goal-eosinophilic-granulomatosis-polyangiitis-egpa-fasenra.html. [Last accessed: October 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 news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html#. [Last accessed: October 2024]. 

10. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html#. [Last accessed: October 2024]. 

11. AstraZeneca Annual Report 2023. Available at: https://www.astrazeneca.com/content/dam/az/Investor_Relations/annual-report-2023/pdf/AstraZeneca_AR_2023.pdf. [Last accessed: October 2024]. 

12. AstraZeneca news release. Available at: https:// www.astrazeneca.com/media-centre/press-releases/2024/fasenra-approved-in-china-for-the-treatment-of-severe-eosinophilic-asthma.html. [Last accessed: October 2024].

13. Fasenra (benralizumab) US prescribing information; September 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761070s021lbl.pdf [Last accessed: October 2024].

14. AstraZeneca Data on file. 2024. REF- 244520.

15. Wechsler ME, et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017:376;1921-1932.

16. Baldini C, et al. Clinical Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis Clin N Am. 2010;36:527–543.

17. 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.

18. AstraZeneca data on file. 2024. REF-235794.

19. 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: October 2024].  

20. 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: October 2024].