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Phase 2b Data Shows Amlitelimab’s 68-Week Safety for Atopic Dermatitis
Amlitelimab shows promise as a safe and effective treatment for moderate-to-severe atopic dermatitis, with sustained benefits post-treatment.
The phase 2b STREAM-AD trial, presented at SDPA 2025 in Washington, DC, demonstrated an acceptable safety profile of amlitelimab in patients with moderate-to-severe atopic dermatitis (AD) over 68 weeks.1 The trial also showed the effectiveness of amlitelimab over 52 weeks.
“Amlitelimab shows potential to be an effective treatment for patients with moderate-to-severe AD, with sustained clinical response results after they have stopped treatment, supporting the viability of extended dosing, which could decrease treatment burden,” wrote investigators during the publication of the second part of their trial.2
Led by Stephan Weidinger, MD, PhD, dermatology professor at Christian-Albrechts-University and from the University Hospital Schleswig-Holstein in Germany, investigators sought to assess the safety of amlitelimab in patients with moderate-to-severe AD.1 The primary endpoint was percent change in EASI at week 16, and secondary endpoints included the efficacy and safety profile of amlitelimab at weeks 24 and 52, along with just the safety profile at week 68.
Amlitelimab, a fully human, non-depleting anti-OX40L monoclonal antibody, blocks upstream OX40L on antigen-presenting cells. This drug also inhibits T-cell-dependent inflammation without T-cell depletion.
The study had 3 parts: at 24 weeks, 28 weeks, and the 16-week follow-up. Part 1 randomized participants 1:1:1:1 to receive amlitelimab at 500 mg LD (n = 77), 250 mg + placebo LD, (n = 78) 125 mg + placebo LD (n = 77), 62.5 mg + placebo LD (n = 79), and NA + placebo LD (n = 79). In part 1, rates of treatment-emergent adverse events (TEAEs) were similar between the amlitelimab arms, with no observed dose effect. Most reported TEAEs were mild or moderate in the amlitelimab (96.2%) and placebo (95.9%) arms
Part 2 re-randomized participants 3:1, with participants either withdrawn from amlitelimab (placebo; n = 130), continuing amlitelimab at the same dose (n = 44), or continuing placebo (n = 16). Again, most TEAEs were mild to moderate in severity for patients on amlitelimab (96.3%) and placebo (99.1%). No deaths occurred.
Overall, TEAES occurred among 84.6% on amlitelimab 250 mg with 500 mg LD (vs 88.2% switched to placebo), 81.8% among 250 mg with no LD (vs 96.4% switched to placebo), 91.7% on amlitelimab 125 mg (vs 93.8% switched to placebo), and 71.4 on amlitelimab 62.5%. In the placebo arm, 93.3% had TEAEs.
Across 68 weeks, patients on amlitelimab had mild to moderate TEAEs: upper respiratory tract infection (16.3%), headache (16.3%), nasopharyngitis (14%), accidental overdose (9.3%), COVID-19 (9.3%), and dizziness (7%). TEAE leading to treatment discontinuation only occurred for 1 participant on amlitelimab 125 mg.
Serious adverse events (SAE) occurred in 6 participants: 1 participant on amlitelimab 250 mg with 500 mg LD, 1 participant who was on amlitelimab 250 mg with 500 mg LD but switched to placebo, 2 participants who were on amlitelimab 250 mg no LD but switched to placebo, and 1 on amlitelimab 125 mg. Participants on amlitelimab experienced umbilical hernia and ankle fracture. Among participants on and placebos, SAEs included tendon rupture, rotator cuff syndrome, abnormal weight loss, and osteoarthritis.
The team identified 1 SAE related to amlitelimab or placebo by a blinded investigator. This was seen in the 250 mg (no LD) amlitelimab withdrawal arm, and this was not resolved. After occurring on day 400, the participant’s last dose of amlitelimab was on day 141.
The study had low reports of the following TEAEs: nausea, conjunctivitis, and herpes. There were no reported TEAEs of treatment-related anaphylactic reactions, malignancy, serious site reactions, opportunistic infections, pyrexia/chills within 72 hours of injection, and aphthous ulcers.
The team concluded that ongoing trials, including OCEANA phase 3 trials and the long-term extension studies of ATLANTIS, RIVER-AD, and ESTUARY, will provide additional safety data.
“A linear dose-response relationship was not observed, although amlitelimab in a dose of 250 mg plus the LD generally showed numerically greater improvements in secondary end points than did other doses at week 24,” investigators wrote.2
References
Weidinger S, Blauvelt A, Papp KA, et al. Phase 2b randomized clinical trial of amlitelimab, an anti-OX40 ligand antibody, in patients with moderate-to-severe atopic dermatitis. J Allergy Clin Immunol. 2025;155(4):1264-1275. doi:10.1016/j.jaci.2024.10.031
Weidinger S, Gold L, Kataoka Y. 68-Week Safety Results of Amlitelimab (An Anti-OX40 Ligand Antibody) in Participants with Moderate-to-Severe Atopic Dermatitis from STREAM-AD Phase 2b Dose-ranging and Withdrawal. Presented at Society of Dermatology Physician Assistants (SDPA) 2025 in Washington, DC, from June 25 – 28, 2025.
