Understanding EGPA: The role of eosinophils and advancement in treatment options

Eosinophilic granuloma with polyvasculitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare autoimmune disease characterized by moderate-sized blood vessels and eosinophilic phage-infiltrating small blood vessels and tissues and organs. Symptoms of EGPA may vary among patients and may include shortness of breath, sinus problems including nasal polyps, rash, neuropathy, and fatigue.^1-3 EGPA may be difficult to identify because the clinical manifestations may be very heterogeneous.

Although the exact incidence and prevalence rates are not yet known, an estimated 118,000 people worldwide suffer from EGPA.⁴ Patients with EGPA may suffer a significant disease burden due to the involvement of multi-organ systems, frequency of recurrence, and adverse events due to standard treatment. Oral corticosteroids (OCS) and immunosuppressants have been the main pillars of management of EGPA, but the disease often remains uncontrollable or recurs. Furthermore, these drugs may be associated with adverse effects.^3,5-7 This highlights the unmet need for effective treatment options that can help address disease activity and inflammation, aiming to achieve relief and reduce recurrence.

Fasenra® (Benralizumab): Targeted treatment options for EGPA

Fasenra® (benralizumab) injection volumes for subcutaneous use are approved for the treatment of EGPA adults. For the treatment of EGPA, the recommended dose of Fasenra is 30 mg (one injection) and is administered subcutaneously every 4 weeks.⁸

The U.S. FDA approval of Fasenra stems from the positive results of the Mandara Phase III trial. The Mandara clinical trial is a 52-week, randomized, double-blind, actively controlled, positive non-efficiency trial comparing the efficacy and safety of Fasenra vs. Mepolizumab in adult patients with relapsed or refractory EGPA. In addition to continuous background treatment, 140 patients were randomly assigned 1:1 every 4 weeks, and received 30 mg of fasenra or 300 mg of mepolizumab every 4 weeks. The Mandara trial was not intended to assess whether Fasenra is superior to mepolizumab.^8,9

The primary endpoint of Mandara was the proportion of patients who were remission, defined as Birmingham Vasculitis Activity Score (BVAS) = 0, OCS doses <= 4 mg/day at weeks 36 and 48. Among patients taking Fasenra, 59% of the response (n = 41) were versus 57% of the patients taking Mepolizumab (n = 40). Fasenra exhibits non-inferiority against merolizumab, the primary endpoint of relief and the component of relief.^8-9 Just because there is no pre-specified multiple test procedure, there are several secondary endpoints that are descriptive.

During the 48-52 weeks, 41% of patients taking Fasenra had a 100% reduction in OC dose (n = 29), while 26% of patients taking mepolizumab (n = 18). Please note that according to the protocol, OCS dose is at the discretion of the investigator from week 4.^8-9 It is important not to suddenly stop systemic or inhaled corticosteroids after starting treatment with Fassenla. If appropriate, gradually reduce corticosteroids.

In Mandara's study, blood eosinophilia was seen at the first observed time point (week 1) and maintained throughout the 52-week treatment period.⁸ The results are descriptive only.

Fasenra's mechanism of action leads to almost complete depletion of eosinophils.⁸ The mechanism of action of Fasenra in asthma and EGPA has not been determined.

The incidence of adverse reactions in the Mandala study was consistent with the incidence of reactions reported in asthma, but headaches were apart from headaches, which occurred in 17% of Fasenra patients with EGPA. No new adverse reactions were found. The most common adverse reactions of Fasenra (greater than or equal to 5%) include headaches and pharyngitis.

Solve unmet Fasenra's needs

Fasenra provides a treatment option for adults with EGPA that can help meet unmet needs.

The use of Fasenra for the treatment of EGPA is a step forward for healthcare professionals who seek effective ways to manage such challenging conditions. With its unique mechanism of depleting eosinophils and reducing inflammation, Fasenra offers a once-month (every 4 weeks) treatment option with the potential to help patients with EGPA.

Important security information

Contraindications

Hypersensitivity to methylbenzolizumab or excipients are known.

Warnings and preventive measures

Hypersensitivity reaction

Hypersensitivity reactions (e.g., allergic reactions, angioedema, urticaria, rash) occur after administration. These reactions usually occur within a few hours of administration, but in some cases delayed onset (i.e., days). If an allergic reaction occurs, stop production.

Symptoms or worsening of acute asthma

Fasenra should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Lower corticosteroid dose

Do not stop systemic or inhaled corticosteroids suddenly after starting treatment with Fasenra. If appropriate, the reduction in corticosteroid dose should be carried out step by step and under the direct supervision of the physician. The reduction in corticosteroid dose may be associated with symptoms of systemic withdrawal and/or the disclosure of diseases previously inhibited by systemic corticosteroid treatment.

Parasitic (worm) infection

It is unknown whether Fasenra will affect patients' response to worm infection. Treat patients with pre-existing helminth infection before treatment with Fasenra. If the patient is infected while receiving Fasenra and does not respond to anti-spiral treatment, disable Fasenra until the infection resolves.

Adverse reactions

The most common adverse reactions (occur rate ≥5%) include headache and pharyngitis.

The incidence of injection site responses (e.g., pain, erythema, pruritus, papules) was 2.2%, in patients treated with Fasenra, and 1.9% in patients treated with placebo among patients with asthma.

Use in specific groups

Data on pregnancy exposure in clinical trials are insufficient to inform drug-related risks. During the three months of pregnancy, monoclonal antibodies, such as benralizumab, are transported throughout the placenta; therefore, the potential impact on the fetus may be greater during the third month of pregnancy.

Indications

Fasenra's instructions are:

• Additional maintenance treatment for patients with severe asthma age 6 years and older with an eosinophilic phenotype. Fasenra's relief is not suitable for acute bronchospasm or asthma states
• Adult patients with eosinophilic granuloma suffer from polyvasculitis (EGPA)

Please read all Prescription informationinclude Patient information exist www.fasenrahcp.com.

You can Report side effects related to AstraZeneca products (Open a new window).

To learn more about how Fasenra can help support EGPA patients, visit Fasenrahcp.com.

refer to

1. American partnership for eosinophilic diseases. Eosinophilic granuloma with polyvasculitis. Visited on March 26, 2025.
2. Baldini C, Talarico R, Della Rossa A, Bombardieri S. Clinical manifestations and treatment of Churg-Strauss syndrome. Rheumatology clinics in the north. 2010; 36(3): 527-543.
3. Chakraborty RK, Aeddula nr. Eosinophilic granuloma and polyangiovascular (Churg-Strauss syndrome). exist: Statpearls [Internet]. Statpearls Published; September 19, 2024.
4. Data on the file. Ref-244520. Astrazeneca Pharmaceuticals LP.
5. Chung SA, Langford CA, Maz M, etc. 2021 American College of Rheumatology/Vascularitis Foundation Guidelines for Anti-tumor Cytoplasmic Antibody-associated Vasculitis. Arthritis rheumatism. 2021; 73 (8): 1366-1383. doi:10.1002/art.41773.
6. Hellmich B, Sanchez-Alamo B, Schirmer JH et al. EULAR recommendations for ANCA-related vasculitis management: Updated in 2022. Ann Rheum Dis. 2024; 83(1): 30-47. doi:10.1136/ard-2022-223764.
7. Emmi G, Bettiol A, Gelain E, etc. Evidence-based guidelines for the diagnosis and treatment of eosinophilic granuloma by polyvasculitis. Nat Rev Rheumatol. 2023; 19(6): 378-393. doi:10.1038/s41584-023-00958-W.
8. Fasenra® (Benralizumab) [prescribing information]. Wilmington, Germany: AstraZeneca Pharmaceuticals LP; September 2024.
9. Wechsler ME, Nair P, Terrier B et al.; Mandala Research Group. Thyroidzumab and thylizumab are accompanied by eosinophilic granuloma polyangitis. N Engl J Med. 2024; 390(10):911-921.

US-94552 last updated 3/25