S382 Long-Term Safety of Budesonide Oral Suspension for Eosinophilic Esophagitis: An Integrated Safety Analysis of Phase 1–3 Clinical Trial Data

Abstract

Introduction: Budesonide oral suspension (BOS) is an immediate-release swallowed topical corticosteroid developed for eosinophilic esophagitis (EoE). We present an integrated safety analysis of all clinical trials of BOS to provide the largest set of safety data on a topical corticosteroid for EoE to date. Methods: Data were pooled from 6 trials (phase 1, SHP621-101; phase 2, MPI 101-01, MPI 101-06; phase 3, SHP621-301, SHP621-302 and SHP621-303) for all participants who received ≥1 dose of BOS (any trial) or induction placebo (MPI 101-01/MPI 101-06/SHP621-301). For the ongoing open-label study SHP621-303, data were collected until August 14, 2020 (interim data cut-off). Treatment groups were BOS 2.0 mg b.i.d., BOS any dose (including BOS 2.0 mg b.i.d.) and placebo. Adverse events (AEs), clinical laboratory testing, vital-sign monitoring and physical examinations were assessed (all trials). Dual-energy X-ray absorptiometry (DXA) (participants 11–17 years old) and adrenocorticotropic hormone (ACTH) stimulation tests (all participants) were performed in the phase 3 studies. Exposure-adjusted incidence rates were calculated for AEs and AEs of special interest (AESIs); AESIs were categorized as infections, systemic effects of corticosteroids, or gastrointestinal effects. Results: Overall, 514 unique participants were included (BOS 2.0 mg b.i.d., n=292; BOS any dose, n=448; placebo, n=168). The BOS 2.0 mg b.i.d., BOS any dose and placebo groups totaled 87.2, 116.0 and 25.0 patient-years of exposure, respectively. BOS was well tolerated; most treatment-emergent AEs (TEAEs) were mild/moderate in severity (Table 1). The most common exposure-TEAEs (≥5% participants) and AESIs were upper respiratory tract infection, nasopharyngitis and sinusitis; TEAEs, AESIs and AEs leading to study or study drug discontinuation were more common in BOS- than placebo-treated participants (Table 1). AESIs of abnormal ACTH stimulation test and decreased blood cortisol were more frequent in the BOS 2.0 mg b.i.d. and BOS any dose groups (Table 1); most were mild/moderate and without other signs of adrenal insufficiency. DXA scans demonstrated no effect on growth (n=26); the intra-age distribution of TEAEs was similar for the BOS 2.0 mg b.i.d. and BOS any dose groups for participants 11–17 and ≥18 years old (data not shown). One death occurred (unrelated to BOS 2.0 mg b.i.d.). Conclusion: BOS was well tolerated, including at the highest dose (2.0 mg b.i.d.) and for maintenance therapy. Most TEAEs were mild/moderate in severity.Table 1.: Summary Of TEAEs, Exposure-Adjusted TEAEs Per 100 Patient-Years Experienced By ≥5% Of Participants In Any Treatment Group And Exposure-Adjusted AESIs Per 100-Patient Years,* By Preferred Term†.