Fasenra Recommended in Europe for Rare Blood Vessel Disorder

The European Commission has approved the Committee for Medicinal Products for Human Use (CHMP) recommendation to change the terms of marketing authorization for Fasenra (benralizumab). It can now also be used as an add-on treatment in adults with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA). Its original indication is as an add-on maintenance treatment in adults with severe eosinophilic asthma that is inadequately controlled despite high-dose inhaled corticosteroids plus long-acting beta‑agonists.

EGPA is a rare inflammatory condition that affects small to medium-sized blood vessels and can lead to life-threatening damage to multiple organs. The condition often develops in stages. In adolescence and young adulthood, patients often experience allergies, asthma, and sinus symptoms. Later, patients develop eosinophilia and vasculitis, often preceded by weight loss, tiredness, and fever. There are around 12 cases of EGPA per million individuals in Europe. 

Fasenra’s active substance, benralizumab, binds to and blocks the effects of interleukin 5 receptor subunit alpha, reducing the production and survival of eosinophils. It also activates another receptor, FcγRIIIa, located on natural killer cells. This enhances programmed cell death of eosinophils and the apoptosis of basophils, a type of white blood cell that has a critical role in asthma-related airway inflammation.

The CHMP’s recommendation is based on results from the MANDARA phase 3 trial, which compared efficacy and safety of benralizumab vs mepolizumab, the only approved treatment for EGPA, in patients with relapsed and refractory EGPA. For the trial, 140 patients were randomly assigned to receive 30 mg benralizumab or 300 mg mepolizumab via subcutaneous injection every 4 weeks for 52 weeks. 

The primary clinical endpoint was remission at weeks 36 and 48; secondary endpoints included the overall remission duration, time to first relapse, oral glucocorticoid use, eosinophil count, and safety. 

At week 36 and 48, 59% of patients taking benralizumab and 56% of those taking mepolizumab were in remission, showing noninferiority but no superiority of benralizumab to mepolizumab. 

Both groups experienced similar overall remission durations; however, 41% of those taking benralizumab and 26% of those receiving mepolizumab completely withdrew from oral glucocorticoids between weeks 48 and 52.

Mean blood eosinophil count started at 306.0 ± 225.0 cells/µL in the benralizumab group and 384.9 ± 563.6 cells/µL in the mepolizumab group and decreased to 32.4 ± 40.8 and 71.8 ± 54.4 cells/µL at week 52, respectively.

Both drugs had similar safety and tolerability profiles. Adverse events were reported among 90% of patients taking benralizumab and 96% taking mepolizumab. The most common adverse events included COVID-19, headache, and arthralgia. 

Serious adverse events occurred in 6% of those taking benralizumab and 13% of those taking mepolizumab; these included COVID-19 and prostate cancer. There were no deaths. 

The trial has an ongoing open-label extension period. 

The recommended dose of benralizumab for EGPA is 30 mg by subcutaneous injection every 4 weeks. Patients who develop life-threatening manifestations of the condition should be evaluated for a decision on whether to continue therapy, as the drug has not been studied in this population. The safety and efficacy of Fasenra have also not been established in children and adolescents younger than 18 years.

Annie Lennon is a medical journalist. Her writing appears on Medscape Medical News, Medical News Today, and Psych Central, among other outlets.