Durable maintenance of EASI-90 with amlitelimab in adults with moderate-to-severe atopic dermatitis: 52-week results from the STREAM-AD phase 2b trial

Abstract

Introduction & Objectives: Amlitelimab (SAR445229, KY1005) is a fully human, anti-OX40 ligand (OX40L) monoclonal antibody. In the STREAM-AD phase 2b trial (NCT05131477), the primary endpoint was met at Week 16, with a significant decrease in Eczema Area and Severity Index (EASI) percentage change with amlitelimab versus placebo. Amlitelimab demonstrated clinically meaningful improvements in atopic dermatitis (AD) lesions and pruritus compared with placebo-treated participants up to Week 24 in Part 1, including the proportion of patients achieving ≥90% improvement of EASI (EASI-90). In clinical responders, defined as participants achieving EASI-75 and/or Investigators Global Assessment (IGA) 0/1 at Week 24, durability of response (EASI-75 and IGA 0/1) was observed through Week 52 (Part 2), with improvements maintained while participants were either on- or off-amlitelimab. Here, the proportion of clinical responders achieving and maintaining EASI-90 with amlitelimab in Part 2 of the STREAM-AD trial is reported.

Materials & Methods: STREAM-AD was a 52-week, randomised, double-blinded, placebo-controlled trial, consisting of a 24-week treatment period (Part 1) and a 28-week maintenance/withdrawal period (Part 2). Adults with moderate-to-severe AD (N=390) were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab every 4 weeks (Q4W; 250 mg + 500-mg loading dose [LD], n=77; 250 mg, n=78; 125 mg, n=77; or 62.5 mg, n=79) or placebo Q4W (n=79) in Part 1. In Part 2, clinical responders (N=190) were re-randomised 3:1 to withdraw from amlitelimab or continue their pre-Week 24 dose (250 mg with 500-mg loading dose, n=34 [treatment withdrawal]/n=13 [continuing]; 250 mg, n=28/n=12; 125 mg, n=33/n=12; 62.5 mg, n=35/n=7; placebo responders continuing placebo, n=16) for 28 weeks. Among overall clinical responders (participants achieving EASI-75 and/or IGA 0/1 at Week 24), the proportion of patients who achieved EASI-90 at Week 24 and maintained it at Week 52 following continuation or withdrawal from amlitelimab during Part 2 (post hoc) was evaluated. Participants using rescue medications in Part 2 or with missing data were imputed as non-responders.

Results: Among overall amlitelimab-treated clinical responders, 62.6% achieved EASI-90 at Week 24. Among these Week 24 EASI-90 responders, 61.3% of participants who continued amlitelimab during Part 2 maintained EASI-90 at Week 52. Of the Week 24 EASI-90 responders who withdrew from amlitelimab for 28 weeks, 59.0% maintained EASI-90 at Week 52.

Conclusions: The results demonstrate that a high proportion of clinical responders achieved EASI-90 response at Week 24. The majority maintained EASI-90 response with continued amlitelimab treatment at Week 52. Notably, EASI-90 was also maintained at Week 52 after 28 weeks of withdrawal from amlitelimab by the majority of Week 24 EASI-90 responders. Taken together, these data further demonstrate that targeting the OX40L/OX40 pathway via amlitelimab may lead to durable disease control, even while off-amlitelimab, in patients with moderate-to-severe AD. Ongoing phase 3 trials will further evaluate the effect of continued amlitelimab treatment or withdrawal over longer observational periods.