⚡A First for Chronic Hand Eczema

Good morning — it’s Saturday, August 9, and we’re covering the first FDA-approved therapy for chronic hand eczema, new Phase 3 results for upadacitinib in alopecia areata, and more.

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LEO Pharma’s delgocitinib cream (Anzupgo) is now the first treatment approved by the US FDA for moderate-to-severe chronic hand eczema in adults.

The pan-JAK inhibitor targets JAK1/2/3 and TYK2, disrupting the JAK-STAT signaling pathway.

Approval was supported by the Phase 3 DELTA 1 and 2 trials. These studies enrolled 960 adults with moderate-to-severe disease and an inadequate response or contraindication to topical corticosteroids.

At Week 16, 20% and 29% of delgocitinib-treated patients achieved clear or almost clear skin (IGA 0/1 with ≥2-point improvement), compared to 10% and 7% with vehicle (both P ≤ 0.0055). Safety was comparable between groups.

The DELTA 3 extension study followed 801 patients who completed the pivotal trials. Among those initially randomized to delgocitinib, IGA-CHE 0/1 response was maintained at 30% through Week 52. Notably, 81% of patients who stopped delgocitinib after achieving a good response regained disease control upon retreatment for disease worsening.

Earlier this year, topical delgocitinib outperformed oral alitretinoin in the DELTA FORCE trial published in The Lancet. By Week 12, 39% delgocitinib-treated patients achieved at least a 90% reduction in hand eczema severity (HECSI-90), compared to 26% on alitretinoin (P = 0.003). Safety also favored delgocitinib, with adverse events in 49% of patients versus 76% with alitretinoin.

The drug is already approved in the European Union, United Kingdom, and United Arab Emirates.

AbbVie announced that upadacitinib (Rinvoq) met all primary and key secondary endpoints for severe alopecia areata in Study 2 of the Phase 3 UP-AA program. A companion trial (Study 1) with an identical design is ongoing.

Investigators randomized patients with a mean SALT score of 84 (indicating ~16% scalp hair coverage) to daily upadacitinib (15 mg or 30 mg) or placebo.

By Week 24, 45% and 54% of patients in the 15 mg and 30 mg groups achieved at least 80% scalp hair coverage (SALT score ≤20), compared to just 3% on placebo (P < 0.001).

A stricter target (SALT ≤10) was reached by 36% and 47% of upadacitinib-treated patients, versus 1% with placebo (P < 0.001).

Both doses also significantly improved eyebrow and eyelash regrowth.

Safety findings aligned with prior studies. Serious adverse events occurred in 1% of patients in the 15 mg group and 3% in the 30 mg group. One patient in the 15 mg group with multiple risk factors experienced a venous thromboembolism.

Study 1 results are expected later this year. Combined, the two trials have enrolled 1,399 patients.

Upadacitinib is already approved for moderate to severe atopic dermatitis and is also in Phase 3 trials for hidradenitis suppurativa and vitiligo.

> Daily full-body emollient use from early infancy reduces 2-year incidence of atopic dermatitis in infants: Data from the CASCADE trial, published in JAMA Dermatology, suggest that daily full‑body emollient application from early infancy may lower atopic dermatitis risk. This pragmatic trial enrolled 1,247 infants from 25 US community‑based clinics. Infants were randomized to one of two groups: daily full-body emollient application starting by 9 weeks, or no routine emollient use. At age 2 years, the cumulative incidence of atopic dermatitis was lower in the emollient group than in the control group (36% vs 43%; RR 0.84, 95% CI 0.73–0.97; P = 0.02). The protective effect was greater in low‑risk infants (RR 0.75, 95% CI 0.60–0.90) than in high‑risk infants (RR 0.93, 95% CI 0.80–1.10), with high‑risk defined as having a first‑degree relative with atopy. A stronger effect was also observed in households with a dog (RR 0.68, 95% CI 0.50–0.90). In contrast, PreventADALL, another large emollient trial that enrolled infants regardless of atopy risk, found no preventive effect. However, its intervention involved baths with emulsified oil followed by cream applied only to the face for nine months.

> EU approves first treatment for NF1-associated plexiform neurofibromas in adults and children: The European Commission has conditionally approved mirdametinib (Ezmekly) as the first treatment for symptomatic, inoperable plexiform neurofibromas in both adults and children aged 2 years and older with neurofibromatosis type 1 (NF1). Affecting up to 30–50% of NF1 patients, these tumors cause significant morbidity and may undergo malignant transformation. Up to 85% are not amenable to complete surgical resection. The approval followed results from the ongoing single-arm Phase 2b ReNeu trial, which enrolled 114 patients. Mirdametinib achieved median tumor volume reductions of more than 40% in both adults and children. Among responders, 88–90% maintained their response for at least 12 months. Common adverse events included acneiform rash, diarrhea, nausea, and vomiting in both age groups; paronychia was also frequent in children. Treatment discontinuations due to adverse events occurred in 22% of adults and 9% of children. Mirdametinib is a selective MEK1/2 inhibitor that targets MAPK pathway hyperactivation in NF1. It was approved earlier this year in the United States under the brand name Gomekli.

> Phase 2 study of ME3183 in psoriasis shows encouraging efficacy but high discontinuation rates: The next‑generation oral phosphodiesterase 4 (PDE4) inhibitor ME3183 showed encouraging efficacy in a Phase 2 trial for moderate‑to‑severe psoriasis, but the treatment arm saw high discontinuation rates. Developed by Meiji Pharma USA, ME3183 has stronger in vitro PDE4 inhibition than apremilast. Investigators randomized 132 patients to ME3183 or placebo for 16 weeks, followed by a 4-week observation period. At Week 16, 52–62% of patients receiving ME3183 (5 mg BID, 7.5 mg BID, or 15 mg QD) achieved ≥75% reduction in disease severity (PASI 75), compared to 15% with placebo (all P < 0.01). Clear or almost clear skin (sPGA 0/1) was achieved by 28–50% of patients across ME3183 dose groups, versus 11% with placebo. Despite these results, nearly one‑third of participants discontinued the trial. Discontinuations due to adverse events occurred in 8–19% of patients on ME3183, compared to 4% on placebo. Most adverse events were mild to moderate; diarrhea (16%–39%), headache (8%–42%), and nausea (8%–31%) were the most common.

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In the open-label LIMMitless extension study of 897 adults with moderate-to-severe psoriasis, the IL-23 inhibitor risankizumab maintained high efficacy over six years, with a PASI 100 response rate—indicating complete skin clearance—of 54% at Week 304. Serious adverse events were rare over nearly 5,000 patient-years of exposure (More)

In a randomized split-scalp/face trial of 37 solid organ transplant recipients with actinic keratoses, sequential cryotherapy followed by 1% tirbanibulin ointment led to complete clearance of lesions in 51% of patients at 4 months, compared to 11% with cryotherapy alone (P = 0.001) (More)

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A retrospective study of 59 patients with atopic dermatitis presenting with nummular eczema found that treatment with dupilumab or tralokinumab led to ≥75% improvement in eczema severity (EASI 75) in 67% of patients by Week 16. Among the 37 with Week 52 data, the response rate rose to 87% (More)