Interim Safety Results of Amlitelimab (anti-OX40 ligand antibody) in Participants With Moderate-to-Severe Atopic Dermatitis From the RIVER-AD Phase 2/3 Ongoing Open-Label Study

Abstract

Introduction & Objectives Amlitelimab (SAR445229, KY1005) is a fully human, nondepleting, anti-OX40 Ligand monoclonal antibody. The efficacy and safety of amlitelimab administered subcutaneously every 4 weeks (Q4W) in adults with moderate-to-severe atopic dermatitis (AD) was previously demonstrated in the STREAM-AD phase 2b trial (NCT05131477). At Week 24 of STREAM-AD, clinical responders (defined as achieving at least a 75% improvement in the Eczema Area and Severity Index [EASI-75] and/or an Investigator Global Assessment score of 0 or 1 [IGA 0/1]) were rerandomized to either continue or withdraw from amlitelimab for an additional 28 weeks. The majority of participants maintained durable responses at Week 52 (Part 2) on and off amlitelimab treatment. Participants in the STREAM-AD trial were eligible to enter the RIVER-AD open-label long-term extension study if they met one of the following criteria: 1) did not achieve clinical responses by week 24; 2) lost clinical responses (<EASI-50) during part 2; or 3) completed part 2 and experienced AD worsening during or after the safety follow-up. Additionally, participants with moderate-to-severe AD from other amlitelimab AD clinical trials were eligible to enter RIVER-AD. Here, interim safety results from RIVER-AD are reported for participants who previously had been enrolled in STREAM-AD, with an interim data cutoff date of 20 February 2024.

Materials & Methods RIVER-AD (NCT05492578) is an ongoing phase 2/3, open-label, 332-week extension study evaluating the long-term safety and efficacy of amlitelimab. The use of topical corticosteroids/calcineurin inhibitors is permitted. Based on the cut-off date (20 February 2024), this interim safety analysis includes only participants from STREAM-AD who had entered RIVER-AD and received amlitelimab 250 mg Q4W. Data are presented as number of patients with ≥1 event per 100 patient-years at risk (nP/100 PYR). PYR is calculated as the time from first dosing of amlitelimab to the initial occurrence of an event or end of follow-up/data cutoff for those without any event.

Results This interim safety analysis included 249 participants with a cumulative exposure of 185.7 patient-years. The median treatment duration was 282.0 days (range: 28-548 days), with the following distribution: >0 - ≤20 weeks, 20.9%; >20 - ≤40 weeks, 28.9%; >40 - ≤60 weeks, 36.1%; >60 - ≤80 weeks, 14.1%. At data cutoff, the exposure-adjusted incidence of treatment-emergent adverse events (TEAEs) was 143.1 nP/100 PYR in the safety population, with 144 (57.8%) participants reported to have ≥1 TEAE. The most commonly reported TEAEs (occurring in ≥5% of participants) were nasopharyngitis (16.7 nP/100 PYR), worsening of AD (15.1 nP/100 PYR), and upper respiratory tract infection (10.6 nP/100 PYR). Treatment-emergent serious adverse events and TEAEs leading to treatment discontinuation each occurred in 4 (1.6%) participants (2.2 nP/100 PYR). Adverse events of special interest occurred in 6 (2.4%) participants (3.4 nP/100 PYR). No deaths occurred.

Conclusions In this RIVER-AD phase 2/3 interim safety analysis of adult participants with moderate-to-severe AD originally from the phase 2b STREAM-AD trial, amlitelimab 250 mg Q4W demonstrated an acceptable safety profile generally consistent with what was previously reported in STREAM-AD.