FDA-Approved Asthma Biologics: Mechanisms of Action and Treatment Selection

"FDA-Approved Asthma Biologics: Mechanisms of Action and Treatment Selection" gives viewers a concise tour of the biologic landscape and the reasoning behind choosing among agents.

Dr. Bernstein asks Dr. Chupp to describe the FDA-approved biologics for asthma and their mechanisms. Dr. Chupp confirms that 7 agents are now approved. He offers a quick summary of the class.

The first was omalizumab, an anti-IgE antibody with which clinicians have many years of experience. Roughly a decade passed before mepolizumab became the first approved anti-IL-5 therapy for asthma. Reslizumab arrived around the same time, but because it is given intravenously, it is used less often.

Benralizumab followed shortly after. It is an anti-IL-5 receptor monoclonal antibody dosed every 8 weeks during maintenance. Dupilumab, which blocks the IL-4 receptor to inhibit IL-4 and IL-13 signaling, came around 2018.

Tezepelumab followed as the first approved therapy against an alarmin, soluble TSLP. Dr. Chupp notes it was the first to show significant outcomes in patients with both high and low biomarker levels. Most recently, depemokimab, an ultra-long-acting anti-IL-5 antibody, is dosed every 6 months.

He finds this range exciting. The agents differ in dosing, effectiveness, and ideal candidates, based on phase 3 trial data. If one biologic does not produce an ideal response, clinicians can switch to another.

Dr. Bernstein raises the challenge of treating patients with low eosinophil counts. Dr. Chupp explains that a patient who is not systemic steroid-dependent and has low biomarker levels would be a candidate for tezepelumab, or for omalizumab if allergic. He emphasizes adherence to phase 3 data when prescribing.

Practical features then come into play. Omalizumab may require dosing as often as every 2 weeks, depending on weight and IgE level. Tezepelumab requires 1 injection monthly. During shared decision-making, he notes, patients often prefer to start with the less frequent, single-injection option.

Our next episode, "Early Biologic Therapy in Asthma to Prevent Lung Function Decline," examines the inflammation-exacerbation cycle, as Dr. Wechsler and Dr. Mosnaim make the case for starting biologics sooner.