FASENRA approved in the US for eosinophilic granulomatosis with polyangiitis

Rhea-AI Summary

AstraZeneca's FASENRA (benralizumab) has been approved in the US for treating adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), a rare immune-mediated vasculitis. The approval is based on the MANDARA Phase III trial, which showed:

- Nearly 60% of FASENRA-treated patients achieved remission
- 41% of patients fully tapered off oral corticosteroids
- FASENRA's efficacy was comparable to mepolizumab, the only other approved EGPA treatment

FASENRA is now the second biologic approved for EGPA in the US. It offers a convenient monthly subcutaneous injection and has shown potential to help patients taper off steroid therapy. This approval expands FASENRA's use beyond its existing indication for severe eosinophilic asthma.

Positive

• FDA approval for FASENRA to treat EGPA, expanding its market potential
• Nearly 60% of FASENRA-treated patients achieved remission in the MANDARA trial
• 41% of FASENRA-treated patients fully tapered off oral corticosteroids
• FASENRA's efficacy was comparable to the only other approved EGPA treatment
• FASENRA offers a convenient monthly subcutaneous injection for EGPA patients

Negative

• None.

Medical Research Analyst

This FDA approval for FASENRA in EGPA is a significant development in the treatment landscape. The MANDARA trial results show 60% of patients achieved remission, comparable to the current standard of care. More impressively, 41% of patients were able to fully taper off oral corticosteroids, addressing a major concern in long-term EGPA management.

The ability to reduce steroid use is crucial, as it can mitigate serious side effects associated with prolonged steroid therapy. This new treatment option could potentially improve long-term outcomes and quality of life for EGPA patients, who often struggle with debilitating symptoms and treatment options.

Financial Analyst

This approval opens a new market opportunity for AstraZeneca's FASENRA. While EGPA is a rare disease with an estimated 15,000 patients in the US, orphan drug designations often command premium pricing. The approval in this new indication could drive additional revenue growth for FASENRA, which is already well-established in severe eosinophilic asthma.

Moreover, this expansion into rare diseases aligns with AstraZeneca's strategy to diversify its portfolio. The company's focus on eosinophilic diseases beyond asthma suggests potential for further label expansions in the future, which could contribute to sustained growth in the Respiratory & Immunology segment.

Market Research Analyst

This approval positions FASENRA as only the second biologic approved for EGPA, potentially capturing a significant share of this niche market. The head-to-head trial against the current standard of care, mepolizumab, demonstrates comparable efficacy with the added benefit of a more convenient dosing regimen (single monthly injection vs. three injections).

This could be a key differentiator in the market, potentially driving physician preference and patient compliance. The positive safety profile and established use in severe eosinophilic asthma may also facilitate faster adoption among healthcare providers already familiar with FASENRA, giving AstraZeneca a competitive edge in this rare disease space.

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

WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZeneca’s FASENRA® (benralizumab) has been approved in the US for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).¹ EGPA is a rare, immune-mediated vasculitis that can result in damage to multiple organs, and without treatment, can be fatal.^2,3

The approval by the US Food and Drug Administration (FDA) was based on positive results from the MANDARA Phase III trial published in The New England Journal of Medicine,⁴ which 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.^5,7 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, nearly 60% 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. 26% in the mepolizumab arm (difference: 16%; 95% CI: 1,31)).⁴

Dr. Michael Wechsler, Professor of Medicine and Director of The Asthma Institute at National Jewish Health, and International Coordinating Investigator of the MANDARA trial said: “This approval is great news for patients with EGPA in the US who continue to suffer from debilitating symptoms. Patients often rely on long-term oral corticosteroids, which can cause serious and lasting side effects. Benralizumab is a much-needed treatment option, with data showing that not only is remission an achievable goal for EGPA patients, but benralizumab can also help patients taper off steroid therapy.”

Joyce Kullman, Executive Director, Vasculitis Foundation said: “This disease has a devastating impact on patients and the quality of their life, and they need more treatment options. The approval of another treatment in EGPA is welcome news to the approximately 15,000 patients living in the US with this difficult-to-treat rare disease.”

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca said: “FASENRA is already well established for the treatment of severe eosinophilic asthma, and with this approval, physicians in the US will now be able to offer an important new, convenient single monthly subcutaneous injection to their patients with EGPA. Today’s news demonstrates the potential of FASENRA to help patients suffering from eosinophilic diseases beyond severe asthma.”

The safety and tolerability profile for FASENRA in the MANDARA trial was consistent with the known profile of the medicine.⁴

Approximately half of patients with EGPA have adult-onset severe eosinophilic asthma (SEA) and often have sinus and nasal symptoms.^3,8,9 FASENRA is only the second biologic approved to treat this disease.^4,5

FASENRA is currently approved as an add-on maintenance treatment for SEA in more than 80 countries including the US, Japan, EU, and China.^10-13 It is also approved in children and adolescents ages 6 and above in the US and Japan. The FDA granted Orphan Drug Designation for FASENRA for EGPA in 2018.¹⁴

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Known hypersensitivity to benralizumab or excipients.

WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (ie, days). Discontinue in the event of a hypersensitivity reaction.

Acute Asthma Symptoms or Deteriorating Disease
FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection
It is unknown if FASENRA will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until infection resolves.

ADVERSE REACTIONS
The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis.

Injection site reactions (eg, pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo in asthma exacerbation studies.

USE IN SPECIFIC POPULATIONS
The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

INDICATIONS
FASENRA is indicated for:

• the add-on maintenance treatment of patients with severe asthma aged 6 years and older and with an eosinophilic phenotype. FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus
• the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA)

Please read accompanying Prescribing Information, including Patient Information.

Notes
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 15,000 patients living in the US have EGPA.^15,16 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.^3,17 Without treatment, the disease may be fatal.^3,17 Almost half (47%) of patients do not achieve remission with current treatments.¹⁸

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.^17,19

MANDARA
MANDARA was a Phase III, randomized, double-blinded, active-controlled trial, which compared the efficacy and safety of FASENRA to mepolizumab in adult patients with relapsing or refractory EGPA.⁵ In the trial, 140 patients were randomized 1:1 to receive either a single 30mg subcutaneous injection of FASENRA or three separate 100mg 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 FASENRA versus mepolizumab based on the primary endpoint.⁴

FASENRA
FASENRA (benralizumab) is currently approved in more than 80 countries, including the US, EU, Japan, and China.^10-13 FASENRA has been prescribed to over 130,000 patients globally.²⁰

FASENRA is in development for other diseases including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.^21-23

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

AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease areas and is a key growth driver for the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage. The Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.

AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

References

1. FASENRA (benralizumab) US prescribing information; September 2024.
2. Furuta S, et al. Update on eosinophilic granulomatosis with polyangiitis. Allergol Int. 2019;68:430-436.
3. American Partnership for Eosinophilic Disorders. Eosinophilic Granulomatosis with Polyangiitis (EGPA). Available at: https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/. [Last accessed: September 2024].
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: September 2024].
6. Mepolizumab US prescribing information. Available from: https://www.fda.gov/files/drugs/published/125526-Mepolizumab-Clinical-PREA.pdf [Last accessed: September 2024].
7. 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: September 2024]
8. Cottin V, et al. Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg–Strauss). Eur Respir J. 2016;48:1429-1441.
9. 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.
10. 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: September 2024].
11. 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: September 2024].
12. 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: September 2024].
13. AstraZeneca news release. FASENRA met the primary endpoint in the MANDARA Phase III trial in eosinophilic granulomatosis with polyangiitis (EGPA). Available at: https://www.astrazeneca.com/media-centre/press-releases/2023/fasenra-phase-iii-egpa-trial-met-primary-endpoint.html#:~:text=Positive%20high%2Dlevel%20results%20from,EGPA)%20who%20were%20receiving%20oral. [Last accessed: September 2024].
14. AstraZeneca news release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2018/us-fda-grants-fasenra-orphan-drug-designation-for-eosinophilic-granulomatosis-with-polyangiitis-26112018.html. [Last accessed: September 2024].
15. IQVIA data on file. 2024.
16. AstraZeneca Data on file. 2022. REF-244520.
17. Baldini C, et al. Clinical Manifestations and Treatment of Churg-Strauss Syndrome. Rheum Dis Clin N Am. 2010;36:527–543.
18. Wechsler ME, et al. Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med. 2017:376;1921-1932.
19. 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.
20. AstraZeneca data on file. 2024. REF-235794.
21. 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 2024].
22. 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 2024].
23. 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 2024].

US-90967 Last Updated 9/17

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FAQ

What is the new FDA-approved indication for FASENRA (AZN)?

FASENRA (benralizumab) has been approved by the FDA for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA), a rare immune-mediated vasculitis.

What were the key results of the MANDARA Phase III trial for FASENRA (AZN) in EGPA?

The MANDARA trial showed that nearly 60% of FASENRA-treated patients achieved remission, and 41% of patients fully tapered off oral corticosteroids. FASENRA's efficacy was comparable to mepolizumab, the only other approved EGPA treatment.

How does FASENRA (AZN) administration differ from other EGPA treatments?

FASENRA offers a convenient single monthly subcutaneous injection for EGPA patients, compared to the three separate injections required for mepolizumab, the other approved biologic for EGPA.

What is the significance of FASENRA's (AZN) approval for EGPA patients?

FASENRA is only the second biologic approved to treat EGPA, providing an important new treatment option for the approximately 15,000 EGPA patients in the US. It has shown potential to help patients achieve remission and taper off steroid therapy.