FDA Grants Orphan Drug Designation to AstraZeneca and Amgen's Tezepelumab for Eosinophilic Esophagitis (EoE)

Compiled by | Manman

Recently, AstraZeneca announced that the U.S. FDA has granted orphan drug designation to tezepelumab for the treatment of the rare inflammatory disease eosinophilic esophagitis (EoE).

EoE is a rare chronic inflammatory disease involving a range of inflammatory cells that can cause symptoms such as severe pain and dysphagia in patients. Currently, there are no approved treatments for eosinophilic esophagitis in the United States.

Tezepelumab, co-developed by AstraZeneca and Amgen, is a potential first-in-class drug that targets and blocks thymic stromal lymphopoietin (TSLP). TSLP is an epithelial cytokine produced in response to pro-inflammatory stimuli (such as allergens, viruses, and other pathogens in the lungs). Its expression is increased in the airways of asthma patients and correlates with disease severity. Blocking TSLP prevents immune cells from releasing pro-inflammatory cytokines, thereby preventing asthma exacerbations and improving asthma control.

As early as July this year, the U.S. FDA accepted the Biologics License Application (BLA) for the antibody drug tezepelumab for the treatment of severe asthma and granted priority review.

The Tezepelumab BLA is based on positive data from the PATHFINDER clinical program, including positive results from the pivotal Phase 3 NAVIGATOR trial. The trial demonstrated that, in a broad population of patients with severe, uncontrolled asthma, tezepelumab showed superiority over placebo across all primary and key secondary endpoints.

The NAVIGATOR trial was the first Phase III trial to demonstrate a therapeutic benefit of targeting TSLP in severe asthma. Data showed that across the overall patient population, treatment with tezepelumab + SoC significantly reduced the annualized asthma exacerbation rate (AAER) by 56% over 52 weeks compared with placebo + standard of care (SoC), a difference that was both statistically and clinically significant (AAER: 0.93 vs. 2.10; RR = 0.44; p < 0.001). Compared with placebo, patients treated with tezepelumab demonstrated a significant reduction in AAER regardless of blood eosinophil count, allergic status, or FeNO levels. In this trial, SoC consisted of medium- or high-dose inhaled corticosteroids (ICS) plus one additional controller medication, with or without oral corticosteroids (OCS).

Furthermore, the trial also met its primary endpoint in the subgroup of patients with a baseline eosinophil count <300 cells/μL: treatment with tezepelumab + SoC resulted in a statistically significant and clinically meaningful reduction in AAER compared with placebo + SoC. A similar reduction in AAER was observed in the subgroup of patients with a baseline eosinophil count <150 cells/μL. In this study, tezepelumab was well tolerated in patients with severe asthma, with no clinically meaningful differences in safety outcomes between the tezepelumab and placebo groups.

According to estimates from AstraZeneca and Amgen, the US FDA is expected to issue a decision in the first quarter of 2022 regarding the priority review of tezepelumab for asthma patients in the United States.

Meanwhile, Tezepelumab is also undergoing regulatory review for asthma in the European Union and Japan.

Reference:

1.AstraZeneca: FDA Grants Orphan Drug Designation To Tezepelumab For Eosinophilic Esophagitis

2. Blockbuster New Asthma Drug! AstraZeneca/Amgen's First-in-Class TSLP-Targeting Monoclonal Antibody tezepelumab Receives US FDA Priority Review: Will Trigger Fierce Market Competition!