⚡Biggest updates from EADV 2025

Good morning — it’s Saturday, September 27, and we’re covering key updates from EADV 2025, led by J&J’s oral IL-23 inhibitor in psoriasis, and more.

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Johnson & Johnson presented multiple positive Phase 3 results from the ICONIC program at EADV 2025, strengthening icotrokinra’s bid to become the leading oral systemic for psoriasis. Icotrokinra is a first-in-class oral peptide that blocks the IL-23 receptor.

In the pivotal ICONIC-ADVANCE 1 and 2 trials, icotrokinra outperformed the oral TYK2 inhibitor deucravacitinib across all co-primary endpoints.

By Week 24, 65–66% of patients achieved ≥90% reduction in disease severity (PASI 90), compared with 41–43% on deucravacitinib (P<0.0001). Rates of complete clearance (PASI 100) were more than double those with the comparator (33–41% vs 16%).

Adverse events were similar to placebo and less frequent than with deucravacitinib, particularly for infections.

Complementing these findings, one-year data from the ICONIC-LEAD trial reinforced icotrokinra’s durability in maintaining skin clearance.

After an initial 24-week placebo-controlled phase, adults who responded to icotrokinra were re-randomized to continue or switch to placebo. At Week 52, 84% of PASI 90 responders who continued icotrokinra maintained their response, compared with 21% who switched to placebo (P < 0.001).

Adolescents were not re-randomized and received continuous therapy for the full 52 weeks, with 86% reaching PASI 90.

Safety remained consistent in both adults and adolescents, with no new signals.

With FDA and EMA filings underway, Johnson & Johnson is now positioning icotrokinra beyond competing oral therapies. The company has launched ICONIC-ASCEND, the first trial testing whether an oral therapy can demonstrate superiority over an injectable biologic using ustekinumab as a comparator.

> Oral alternative for hidradenitis suppurativa nears FDA submission: Incyte’s oral JAK1 inhibitor povorcitinib continues to build momentum in moderate-to-severe hidradenitis suppurativa, with new 24-week results from the pivotal STOP-HS1 and 2 trials. Together, the studies enrolled about 1,200 adults. Earlier 12-week data showed that 40–42% of patients achieved HiSCR50 (≥50% reduction in abscess and nodule counts with no increase in abscesses and draining tunnels), compared with 29–30% on placebo, results considered modest at the time. At EADV 2025, however, extension data revealed further gains: nearly 60% of patients on 45 or 75 mg reached HiSCR50 at Week 24. Notably, elimination of draining tunnels (dt100) occurred in 39–51% of patients. Serious adverse events were seen in fewer than 5% of patients, with no major cardiac events or deaths reported. Incyte plans regulatory submissions in Europe and the U.S. later this year. If approved, povorcitinib would offer patients an oral alternative to injectable biologics, potentially reshaping treatment convenience and access.

> First-in-patient trial of multispecific IL-13/IL-17 blocker galvokimig in atopic dermatitis: UCB’s galvokimig, a first-in-class multispecific antibody, met primary endpoints in a Phase 1/2a trial of 47 patients with moderate-to-severe atopic dermatitis. Unlike single-target biologics, galvokimig simultaneously blocks IL-13, IL-17A, and IL-17F, modulating both Th2 and Th17 pathways. The antibody is also engineered for an extended half-life via albumin binding. At Week 52, 65% of patients receiving galvokimig achieved EASI 75 (≥75% improvement in disease severity), compared with just 12% on placebo. Nearly half (47%) reached EASI-90. Common adverse events were mostly mild (rhinitis, nasopharyngitis, headache, dizziness), though one serious case of hemorrhagic diarrhea was considered treatment-related. UCB plans to launch a Phase 2b trial by the end of 2025.

> Temtokibart sustains efficacy after treatment withdrawal in Phase 2b atopic dermatitis trial: LEO Pharma’s temtokibart is taking a novel approach to atopic dermatitis by blocking IL-22RA1, a receptor expressed predominantly on epithelial rather than immune cells. By targeting this pathway, the drug aims to disrupt IL-22–mediated epidermal thickening and barrier dysfunction. In a 16-week Phase 2b dose-ranging study of 262 adults with moderate-to-severe atopic dermatitis, temtokibart achieved a 57–64% mean reduction in EASI (Eczema Area and Severity Index) with the 300–600 mg doses vs 42% with placebo. Notably, responses were sustained through Week 32, 18 weeks after the last dose. Biomarker analyses confirmed that clinical improvement correlated with downregulation of Th2 and Th17/22 signatures, alongside restored expression of barrier-related genes. Safety was favorable, with low incidences of conjunctivitis (2.4%) and herpes (3.3%). Together, these results position temtokibart as a differentiated pathway-directed therapy supporting continued clinical development.

> Sanofi’s dual TNF/OX40L inhibitor advances in hidradenitis suppurativa: Sanofi announced positive topline results from the Phase 2a HS-OBTAIN trial of brivekimig, a dual-target Nanobody^® that inhibits both TNF and OX40L. The study randomized 71 biologic-naïve adults with moderate-to-severe hidradenitis suppurativa to subcutaneous brivekimig 150 mg every two weeks or placebo. The primary endpoint, HiSCR50, was achieved by 67% of brivekimig patients vs 37% on placebo (P=0.003). Bayesian analysis showed a 99% probability of superiority. Key secondary endpoints also favored brivekimig, including HiSCR75 (54% vs 22%; P=0.017) and HiSCR90 (31% vs 9%; P=0.058). Importantly, the mean draining tunnel count fell by 56% with brivekimig but rose by 11% with placebo (P=0.005). Treatment was well tolerated; nasopharyngitis and headache were the only events reported in >10% of patients and more often than with placebo. Dual TNF and OX40L inhibition may offer a promising therapeutic avenue in advanced disease, expanding options beyond TNF-α and IL-17 blockade.

> Delgocitinib expands evidence with adolescent trial and 52-week adult safety data: Two late-breaking EADV 2025 presentations strengthened delgocitinib’s profile in chronic hand eczema, highlighting both efficacy in adolescents and long-term safety in adults. In the Phase 3 DELTA-TEEN trial of 98 adolescents with moderate-to-severe chronic hand eczema, delgocitinib outperformed vehicle. At Week 16, 72% of delgocitinib-treated adolescents achieved HECSI-90 (≥90% improvement in the Hand Eczema Severity Index) versus 38% on vehicle. No serious adverse events were reported, and fewer patients withdrew on delgocitinib than on vehicle. Separately, an integrated safety analysis of five Phase 2b/3 trials (over 1,000 adults, followed for up to 52 weeks) confirmed a favorable long-term profile. The analysis included both the initial treatment phase (delgocitinib cream vs vehicle or oral alitretinoin for 12–16 weeks) and a subsequent as-needed phase (delgocitinib cream for up to 52 weeks). During the initial period, adverse event rates with delgocitinib were similar to vehicle (302 vs 338 per 100 patient-years) and markedly lower than oral alitretinoin (830), declining further in the as-needed phase. The topical pan-JAK inhibitor is already approved in Europe, the UK, and the U.S.

🔁 EADV late breakers covered in earlier issues of The 4mm

APG777: Long-acting IL-13 blocker shows high efficacy in a Phase 2 atopic dermatitis trial (Read)

Denifanstat: Oral FASN inhibitor meets endpoints in a Phase 3 acne trial (Read)

Rezpeg: Treg stimulator shows positive results in a Phase 2b atopic dermatitis trial (Read)

Quizzes, cases, and perspectives to sharpen your clinical eye.

The BE HEARD extension trial demonstrated bimekizumab’s sustained efficacy and safety in hidradenitis suppurativa over three years. Of 556 patients who entered the extension, 367 completed the full duration. At Year 3, HiSCR50 was achieved by 90% of these patients, with HiSCR75/90/100 rates of 81%, 64%, and 50%. Safety remained consistent with no new signals (More)

In a Phase 2a trial of 30 adults with symptomatic dermographism, 93% achieved a clinical response to EVO756 at Week 4, with improvements apparent as early as Week 1. The first-in-class oral agent targets MRGPRX2 on mast cells and sensory neurons. EVO756 is also in trials for chronic spontaneous urticaria and atopic dermatitis (More)

Sanofi’s balinatunfib, an oral TNFR1-selective inhibitor, was evaluated in a 12-week Phase 2b trial of 221 adults with moderate-to-severe psoriasis. Unlike existing anti-TNFs that block both receptors, balinatunfib selectively inhibits the pro-inflammatory TNFR1 pathway while sparing TNFR2, which supports tissue repair and immune regulation. Although the highest dose did not reach statistical significance for the primary endpoint in therapy-naïve patients, other doses showed clinically meaningful, nominally significant improvements. The drug was generally well-tolerated. Sanofi is now positioning balinatunfib for use in combination regimens rather than as monotherapy (More)

In the pooled Phase 3 randomized TRuE-PN1/2 trials of 394 adults with prurigo nodularis, 42% of patients on ruxolitinib 1.5% cream achieved clinically meaningful itch relief (≥4-point reduction on the 0–10 WI-NRS) at Week 12, compared with 28% on vehicle (P=0.0029). Ruxolitinib also led to higher rates of clear or almost clear skin, defined as IGA-CPG-S 0/1 with ≥2-grade improvement (20% vs 7%; P=0.0002). Both efficacy signals were maintained through 24 weeks, and safety findings were favorable (More)