FDA Rejects AstraZeneca's Fasenra Application for Nasal Polyps Indication Due to Insufficient Data

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AstraZeneca's Fasenra (benralizumab) Hits Roadblock in Attempt to Expand Its Indications.

Recently, the FDA issued a Complete Response Letter to AstraZeneca's Fasenra for its nasal polyp treatment indication application, rejecting the application due to the Phase III trial OSTRO data results being insufficiently convincing.

In the clinical trial study named OSTRO, Fasenra achieved two co-primary endpoints and demonstrated strong safety. The primary endpoints of the study included Fasenra's efficacy in reducing nasal polyps compared to placebo after 40 weeks of the trial, as well as the drug’s impact on nasal congestion in patients compared to placebo after the same period. However, it is clear that the OSTRO trial data was not sufficiently convincing for the FDA, which requested additional clinical trial data in a complete response letter. AstraZeneca stated that it is working closely with regulatory authorities to discuss possible next steps.

Chronic Rhinosinusitis with Nasal Polyps is a common disease characterized by inflammation of the mucous membranes in the nasal and sinus cavities. The inflammation is often accompanied by the growth of globular nasal polyps, which eventually obstruct the nasal passages and cause breathing difficulties. Pathophysiologically, the disease is largely caused by eosinophilic infiltration of the tissue.

Fasenra is a monoclonal antibody that directly binds to the IL-5 receptor α on eosinophils and then attracts killer cells to the site to reduce polyps and inflammation. Fasenra has previously been approved by the FDA as an add-on treatment for severe eosinophilic asthma and received orphan drug designation from the FDA.

According to AstraZeneca's annual report, Fasenra’s sales reached $1.26 billion in 2021, a year-on-year increase of 31%. AstraZeneca is also evaluating Fasenra in other eosinophil-related indications, such as atopic dermatitis, bullous pemphigoid, chronic obstructive pulmonary disease, and chronic spontaneous urticaria.

AstraZeneca had hoped to seize a share from the strong competitor Dupixent, but this FDA rejection letter has put Fasenra at a disadvantage in the competition of anti-inflammatory biologics. In the middle of last year, after Sanofi and Regeneron's IL-4/13 antibody Dupixent entered the field, GlaxoSmithKline's competitor IL-5 inhibitor Nucala also received FDA approval.

Currently, AstraZeneca remains committed to bringing the nasal polyp treatment indication for Fasenra to market. A Phase III clinical study, named ORCHID, targeting the same indication is currently underway. The 56-week trial aims to evaluate the safety and efficacy of Fasenra compared to placebo in patients with eosinophilic chronic rhinosinusitis with nasal polyps. Data from the ORCHID study is expected to be released in the second half of 2023.

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