FASENRA approved in the US 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 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

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US-90967 Last Updated 9/17

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