⚡Anti-OX40L falls short in eczema trial

Good morning — it’s Saturday, September 13, and we’re covering amlitelimab’s Phase 3 trial that fell short of expectations, ruxolitinib cream in hand eczema, and more.

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Sanofi’s anti-OX40L antibody amlitelimab met primary and secondary endpoints in the Phase 3 COAST 1 trial for moderate-to-severe atopic dermatitis, but efficacy underperformed expectations.

At Week 24, 36% and 39% of patients on amlitelimab every 4 or 12 weeks achieved EASI-75 (≥75% reduction in eczema severity), compared to 19% on placebo (P<0.001).

However, the 17–20% advantage over placebo fell short of the 37% seen in amlitelimab’s earlier Phase 2b study and the 32–36% benchmark reported with dupilumab (Dupixent).

Amlitelimab is Sanofi’s lead candidate to succeed Dupixent, which generated $14.15 billion in 2024 sales and faces a 2031 patent cliff.

Amlitelimab’s efficacy mirrors that seen with Amgen’s anti-OX40L antibody rocatinlimab, raising broader questions about the therapeutic potential of the OX40/OX40L pathway.

Despite these concerns, amlitelimab offers advantages. Safety findings were favorable, limited mainly to mild injection-site reactions. Its quarterly dosing schedule, with just four injections annually, could also ease treatment burden, and earlier Phase 2b data suggest responses may persist even after therapy is discontinued.

Sanofi’s amlitelimab OCEANA program includes four more Phase 3 trials, with results expected by 2026. These outcomes will be pivotal in clarifying the drug’s role in atopic dermatitis.

Even so, Sanofi’s shares fell nearly 10% on the COAST 1 readout, reflecting concern that amlitelimab may be confined to a second-line or niche role.

Watch a quick breakdown of OX40/OX40L’s role in atopic dermatitis here.

> Ruxolitinib cream shows rapid itch relief and strong efficacy in hand eczema: A Phase 2 trial published in JAAD showed that ruxolitinib cream (Opzelura) delivered rapid and significant efficacy in moderate-to-severe chronic hand eczema not associated with atopic dermatitis. Among 186 randomized patients, 53% on ruxolitinib achieved clear or almost clear skin (IGA-CHE 0/1 with ≥2-grade improvement) at Week 16, compared to just 11% on vehicle (P<0.0001). Clinically meaningful itch relief (≥4-point reduction on the 0–10 NRS) was evident as early as Day 2 and reached statistical significance by Day 7 (27% vs 9%; P=0.0024). By Week 16, over half achieved this outcome (52% vs 23%; P<0.0001). Treatment was well tolerated, with application-site reactions in only 3%. No adverse events were serious or led to discontinuation. Limitations included the small sample size and short duration. The authors noted vehicle-adjusted efficacy exceeded that reported with delgocitinib, a topical pan-JAK inhibitor recently approved for hand eczema, though trial methodologies differed. Ruxolitinib cream is already FDA-approved for mild-to-moderate atopic dermatitis and nonsegmental vitiligo.

> Topical CGB-500 meets Phase 2b endpoints in atopic dermatitis: CAGE Bio announced positive topline results from its double-blind, dose-ranging Phase 2b trial of CGB-500 in atopic dermatitis. CGB-500 is a topical formulation of the JAK inhibitor tofacitinib combined with an ionic-liquid carrier, which is designed to enhance stratum corneum penetration and deliver systemic-level efficacy with a topical safety profile. The 12-week study enrolled 180 patients aged ≥12 years across the US. Most (~85%) had moderate atopic dermatitis at baseline, all with <10% body surface area involvement. Clear or almost clear skin (IGA 0/1 with ≥2-grade improvement) was achieved by 59% of patients. Itch responses were also strong, with 71% reporting a ≥4-point reduction in itch severity (PP-NRS, 0–10 scale). Over a third (35%) experienced complete itch resolution. Results were statistically superior to vehicle, though vehicle response rates were not disclosed. Treatment was well tolerated with no new safety signals. CAGE Bio plans to advance CGB-500 into Phase 3 and present full results at an upcoming scientific meeting.

> Bimekizumab sets new benchmark for concurrent skin and nail clearance in psoriasis: A post-hoc analysis of three Phase 3 trials (BE SURE, BE VIVID, and BE RADIANT) and their open-label extensions found bimekizumab outperformed adalimumab, ustekinumab, and secukinumab in achieving concurrent skin and nail clearance in moderate-to-severe psoriasis. Adults were included in the analysis if they had any fingernail involvement at baseline (mNAPSI >0) and entered the open-label extension. Concurrent clearance was defined as PASI 100 (complete skin clearance) plus mNAPSI 0 (clear nails). By the end of the comparator periods, bimekizumab outperformed adalimumab (46% vs 18% at Week 24), ustekinumab (51% vs 27% at Week 52), and secukinumab (63% vs 36% at Week 48). In the extensions, clearance was sustained in patients continuously on bimekizumab (52–58%) and improved in those switching from comparators (48–57%) across 3–4 years of follow-up. A key limitation is that only patients who entered the extensions were analyzed, raising the possibility of selection bias. These findings highlight dual IL-17A/IL-17F blockade as a compelling strategy for durable, multi-domain psoriasis control.

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