FDA approves Benralizumab for eosinophilic granulomatosis with polyangiitis

AstraZeneca's Fasenra (benralizumab) has been approved in the US for the treatment of adult patients with 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.

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, which compared the efficacy and safety of Fasenra to the only approved EGPA treatment, mepolizumab, in patients with relapsing or refractory EGPA. MANDARA was the first head-to-head non-inferiority trial of biologics in patients with EGPA. 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.

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)).

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.

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

Fasenra is currently approved as an add-on maintenance treatment for SEA in more than 80 countries including the US, Japan, EU and China. It is also approved in children and adolescents ages six and above in the US and Japan. The FDA granted Orphan Drug Designation for Fasenra for EGPA in 2018.

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. It is estimated that 118,000 people throughout the world live with EGPA and approximately 15,000 patients living in the US have EGPA. 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. Without treatment, the disease may be fatal. Almost half (47%) of patients do not achieve remission with current treatments.

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.

MANDARA

MANDARA was a Phase III, randomised, double-blinded, active-controlled trial, which compared the efficacy and safety of Fasenra to mepolizumab in adult patients with relapsing or refractory EGPA. In the trial, 140 patients were randomised 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.

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. A secondary endpoint was the proportion of patients who were able to fully taper off OCS at weeks 48 through 52. The primary statistical analysis was to demonstrate non-inferiority of Fasenra versus mepolizumab based on the primary endpoint.

Fasenra

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

Fasenra is in development for other diseases including chronic obstructive pulmonary disease, chronic rhinosinusitis with nasal polyps and hypereosinophilic syndrome.

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