Takeda's BOS Achieves Clinical Endpoints in First U.S. Pivotal Phase 3 Trial for Eosinophilic Esophagitis (EoE)

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Takeda Pharmaceutical Announces on October 28 That TAK-721 (Budesonide Oral Suspension, BOS) Met Co-Primary and Key Secondary Efficacy Endpoints in the First of Two Pivotal Phase III Studies Evaluating Treatment for Eosinophilic Esophagitis (EoE), Demonstrating Statistically Significant Improvements Compared with Placebo. BOS is an investigational, novel mucoadhesive topical corticosteroid formulation currently under development in the United States for the treatment of EoE in adolescents and adults.

This was a randomized, double-blind, placebo-controlled study conducted in adolescent and adult patients with eosinophilic esophagitis (EoE) aged 11–55 years to evaluate the efficacy and safety of BOS treatment over 12 weeks. In the study, patients were randomized in a 2:1 ratio to receive either BOS 2.0 mg or placebo, administered twice daily for 12 weeks. Following a 6-week placebo run-in period, 318 patients received at least one dose of double-blind treatment (BOS, n=213; placebo, n=105). The co-primary efficacy endpoints were histologic response (peak eosinophil count ≤6 eosinophils per high-power field) and dysphagia symptom response (≥30% reduction from baseline to end of treatment in the Dysphagia Symptom Questionnaire [DSQ] score) after the initial 12 weeks of treatment. Key secondary efficacy endpoints included the change in DSQ score from baseline to end of treatment, and a secondary endpoint was the change in the EoE Endoscopic Reference Score (EREFS) from baseline to end of treatment.

Notably, this study represents the first pivotal Phase III trial of an EoE drug successfully completed in the United States and constitutes the largest global clinical trial program for EoE conducted to date.

The results showed that after 12 weeks of treatment, the proportions of histologic responders and dysphagia symptom responders were significantly higher in the BOS treatment group compared with placebo (histologic responder rate: 53.1% vs. 1.0%, p < 0.001; dysphagia symptom responder rate: 52.6% vs. 39.1%, p = 0.024). Regarding key secondary endpoints, the improvement in mean DSQ score from baseline to Week 12 was also significantly greater in the BOS treatment group than in the placebo group (−13.0 points vs. −9.1 points, p = 0.015). Similarly, the improvement in mean EREFS score was significantly greater in the BOS treatment group (n = 202) than in the placebo group (n = 93) (−4.0 points vs. −2.2 points, p < 0.001).

In terms of safety, overall, 61.0% of patients reported treatment-emergent adverse events (TEAEs: 61.0% in the BOS treatment group and 61.0% in the placebo group), and 2.5% of patients experienced TEAEs leading to dose interruption (1.4% in the BOS treatment group and 4.8% in the placebo group). TEAEs occurring in ≥2% of patients in either the BOS treatment group or the placebo group included nasopharyngitis, sinusitis, esophageal candidiasis, oral candidiasis, and upper respiratory tract infection. The incidence of TEAEs of oral or esophageal candidiasis was <5% in the overall study population and in each treatment group. No life-threatening TEAEs or deaths were reported during the study.

Budesonide Molecular Structural Formula (Source: Wikipedia)

Eosinophilic esophagitis (EoE) is a rare, chronic, immune-mediated disease occurring in the esophagus, characterized by eosinophil infiltration that causes inflammation. Over the past decade, understanding of EoE has increased significantly; however, its exact etiology remains unclear, though it is believed to be triggered by various stimuli, including certain food and environmental allergens. Patients with EoE may experience dysphagia and/or odynophagia, leading to discomfort and pain. Uncontrolled EoE can lead to esophageal remodeling and fibrosis, resulting in motility disorders and/or food impaction. Currently, there are no FDA-approved therapies specifically indicated for the treatment of EoE. Current EoE guidelines recommend treatment through elimination of target foods from the patient’s diet, use of proton pump inhibitors, and/or topical corticosteroid formulations.

Budesonide is a glucocorticoid with potent local anti-inflammatory effects. Budesonide oral suspension (BOS) is a locally active, viscous oral formulation of budesonide, specifically developed as an investigational drug for the treatment of eosinophilic esophagitis (EoE). In the United States, the FDA granted orphan drug designation to BOS in 2006 and breakthrough therapy designation for BOS in the treatment of adolescent and adult patients with EoE in May 2016.

Reference Source: First-Ever U.S. Pivotal Phase 3 Clinical Study in Eosinophilic Esophagitis (EoE) Completes: Takeda's Investigational Therapy Meets Co-Primary & Key Secondary Efficacy Endpoints