Benralizumab Brings New Approach to Controlling Eosinophilic Asthma

Jean-Marie Pflomm

When the US Food and Drug Administration (FDA) approved benralizumab (Fasenra) to help treat a rare subtype of asthma in both adults and children 12 years or older, there was a hint of gamble for a promising therapy that hasn’t yet absolutely shown consistency.

Patients with eosinophilic asthma have more frequent asthma attacks that are difficult to manage because symptoms are unresponsive to inhaled corticosteroids. The subtype involves inflammation of the respiratory system triggered by high levels of eosinophils. Interleukin-5 (IL-5) is a cytokine responsible for the growth and maturation of eosinophils.

Benralizumab is an anti-IL-5 antibody that interferes with the production of eosinophils. It was the third anti-IL-5 to be approved by the FDA; the previous 2 being mepolizumab and reslizumab. However, there’s a slightly different pathology to the newest therapy.

“Mepolizumab and reslizumab bind to IL-5, preventing it from binding to the IL-5 receptor, which reduces the production and survival of eosinophils,” Jean-Marie Pflomm, Editor-in-Chief of The Medical Letter, told MD Magazine. “Benralizumab binds to the IL-5 receptor itself, preventing IL-5 from binding to it. This results in eosinophil death.”

Two phase 3 trials, SIROCCO (48 weeks) and CALIMA (56 weeks), investigated the effectiveness of add-on therapy with 30 mg of benralizumab administered subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks. Patients were 12-75 years old with uncontrolled asthma, a baseline blood eosinophil count of 300 cells/mL or more, and took a high-dose inhaled corticosteroid, plus a long-acting beta2-antagonist (LABA), with or without additional asthma-controller medications.

The results of both trials showed benralizumab reduced asthma exacerbation rates significantly.

Another trial, ZONDA (28 weeks) examined the effect of using benralizumab as an add-on therapy with a gradual reduction in corticosteroid usage. Subcutaneous 30 mg benralizumab administered every 4 weeks for 3 doses, then every 8 weeks, or placebo was administered to 220 patients. Oral corticosteroid (prednisone, prednisolone) dose was reduced over a 20-week period by 2.5 mg every 4 weeks in patients who met the criteria for asthma control. By week 28, the reduction in daily corticosteroid use was greater with benralizumab (75%) than with placebo (25%).

“Benralizumab appears to rapidly reduce eosinophil levels and reduce them to a greater extent than mepolizumab and reslizumab do, but whether or not this is significant clinically has not yet been established,” said Pflomm.

Pflomm said the primary benefit of benralizumab is that it can be given less frequently (every 8 weeks) than the other 2 anti-IL-5 antibodies (every 4 weeks).

“Another advantage is that benralizumab is given by subcutaneous injection, rather than by intravenous infusion, like with reslizumab,” Pflomm said. “Subcutaneous injections are quicker to administer and carry a lower risk of complications, such as infection.”

While benralizumab has been approved for children 12 years and older, eosinophilic asthma is rare in children. Pflomm said that when the FDA reviewed the drug for approval, there were not enough patients between 12-18 years to fully determine the drug’s efficacy in that age group.

Future studies of benralizumab will involve less common eosinophilic disorders that more often occur in children, such as eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndromes or eosinophilic esophagitis.

A review of benralizumab for severe eosinophilic asthma was published online in JAMA's Medical Letter on Drugs and Therapeutics.