⚡Anti-KIT in CSU, Povorcitinib for Vitiligo, and Guselkumab in PsA

Good morning — it’s Saturday, June 21, and we’re covering an anti-KIT antibody showing durable off-treatment control in chronic spontaneous urticaria, a JAK1 inhibitor advancing in vitiligo, and more.

First time reading? Sign up here.

Enjoying the newsletter? Share it with a friend or colleague — here’s the link.

P.S. You can send me feedback at [email protected]

Celldex‘s barzolvolimab induced complete responses that were sustained for seven months after treatment cessation in patients with antihistamine-refractory chronic spontaneous urticaria (CSU), according to new Phase 2 data presented at EAACI 2025.

The first-in-class monoclonal antibody binds the receptor tyrosine kinase KIT with high specificity, depleting mast cells and inhibiting their activation by blocking stem cell factor–dependent signaling.

In the trial, 208 patients received subcutaneous injections of multiple doses of barzolvolimab or placebo for 16 weeks, followed by 36 weeks of active treatment with barzolvolimab at 150 mg every 4 weeks (Q4W) or 300 mg every 8 weeks (Q8W). After 52 weeks, patients entered a treatment-free follow-up period through Week 76.

At Week 76—seven months after completing therapy—41% of patients treated with the 150 mg Q4W dose were urticaria free (UAS7=0). Nearly half (48%) also reported no impact on quality of life, as measured by DLQI scores of 0 or 1.

Earlier in the study, barzolvolimab met its primary endpoint at Week 12, with 51% of patients who received 150 mg Q4W achieving complete response, compared to just 6% on placebo. By Week 52, that figure rose to 71%. Efficacy was consistent regardless of prior omalizumab use.

Barzolvolimab was well tolerated, with reversible KIT-related effects including mild neutropenia, hair color changes, and skin hypopigmentation.

Celldex has initiated two global Phase 3 trials in CSU. The drug is also being studied in chronic inducible urticaria, prurigo nodularis, and atopic dermatitis.

Povorcitinib, Incyte’s oral small-molecule JAK1 inhibitor, achieved clinically meaningful repigmentation in extensive nonsegmental vitiligo. Findings from the Phase 2 trial were published this week in JAAD.

Investigators randomized 171 adults with extensive vitiligo to receive daily povorcitinib (15, 45, or 75 mg) or placebo for 24 weeks. Patients then continued on 45 or 75 mg through Week 52.

By Week 24, the percentage improvement in Total Vitiligo Area Scoring Index (T-VASI) was 15–19% across povorcitinib groups, compared to −2% in placebo-treated patients (P < 0.01). Facial VASI (F-VASI) scores also improved significantly (28–36% vs. 5% with placebo; P < 0.01).

Repigmentation progressed steadily without plateau through Week 52. Among patients who started and remained on 45 or 75 mg, 37–38% achieved at least a 50% reduction in total vitiligo severity (T-VASI50). Facial repigmentation was more pronounced, with 56–59% reaching F-VASI75, defined as at least a 75% improvement in facial involvement.

Most patients maintained their gains during a 24-week off-treatment follow-up phase.

Povorcitinib was well tolerated, with no treatment-related serious adverse events. Common adverse effects included mild acne and asymptomatic elevations in blood creatine phosphokinase.

With no FDA approved therapies for vitiligo affecting more than 10% of body surface area, these findings support ongoing Phase 3 trials (STOP-V1/V2) of povorcitinib in extensive disease.

> First IL-23 inhibitor to halt structural joint damage in psoriatic arthritis: At EULAR 2025, Johnson & Johnson announced that guselkumab (Tremfya) is the first IL-23 inhibitor to significantly reduce the progression of structural joint damage in active psoriatic arthritis, based on results from the Phase 3b APEX trial. The study enrolled biologic-naïve adults with active psoriatic arthritis and an inadequate response to standard therapies. Patients received guselkumab every 4 or 8 weeks or placebo. At Week 24, both dosing regimens showed a significantly smaller increase in the modified van der Heijde-Sharp (vdH-S) score, which quantifies radiological joint damage, compared to placebo (P ≤ 0.002). ACR50—defined as ≥50% improvement in tender and swollen joint counts and in at least three of five additional domains—was reached in 41–42% of patients, versus 20% with placebo. Skin clearance was also notable, with 68–73% achieving clear or almost clear skin (IGA 0/1), versus 31% on placebo. Guselkumab is a dual-acting monoclonal antibody that blocks IL-23 and binds CD64 on IL-23–producing cells.

> Lebrikizumab improves eczema severity and dyspigmentation in patients with skin of color: Eli Lilly’s interleukin-13 inhibitor lebrikizumab (Ebglyss) showed strong clinical efficacy in patients with skin of color and moderate-to-severe atopic dermatitis, according to results from the Phase 3b ADmirable trial presented at RAD 2025. The open-label, single-arm study enrolled 90 adolescents and adults with Fitzpatrick skin types IV–VI. At Week 24, 78% of patients achieved at least a 75% reduction in eczema severity (EASI 75), while 54% reached clear or almost clear skin (IGA 0/1). Notably, 73% of Week 16 responders were able to switch from dosing every two weeks to once monthly. Improvements were also seen in 64% of patients with hyperpigmentation and 25% with hypopigmentation. Safety findings were consistent with prior trials, with only one case each of conjunctivitis and injection site reaction. Similar EASI 75 outcomes were observed in the DISCOVER trial, which evaluated dupilumab in patients with skin of color and was also presented at RAD 2025.

> Roflumilast clears facial and eyelid eczema in post hoc analysis: A new post hoc subgroup analysis of the INTEGUMENT-1 and -2 trials found that roflumilast cream 0.15% (Zoryve) significantly improves atopic dermatitis involving the face and eyelids. These sites are both visible and cosmetically sensitive. They are also more vulnerable to steroid-induced side effects. Of the 1,337 patients aged ≥6 years with mild-to-moderate atopic dermatitis who were enrolled in the trials, 567 had facial and 277 had eyelid involvement at baseline. By Week 4, 41% of patients treated with roflumilast in the overall population achieved clear or almost clear skin (vIGA-AD 0/1), compared to 21% on vehicle. Response rates were similarly higher for facial (36% vs. 14%) and eyelid (38% vs. 9%) involvement. By the end of the trial, ≥92% of patients with facial or eyelid involvement reported no or mild application-site sensation. Limitations include the exploratory nature of the analysis and short trial duration. The topical phosphodiesterase-4 inhibitor was approved in July 2024 for patients aged ≥6 years with mild-to-moderate atopic dermatitis.

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

In a real-world registry study of 192 adults with moderate-to-severe atopic dermatitis treated with upadacitinib, 64% of biologic-naïve and 53% of biologic-experienced patients achieved at least a 90% improvement in eczema severity (EASI 90) after 6 months (More)

In a 24-week study of 30 patients with progressive non-segmental vitiligo, combination therapy with oral upadacitinib and ruxolitinib cream resulted in ≥75% facial repigmentation (F-VASI75) in 33% of patients and ≥50% total body repigmentation (T-VASI50) in 20% of patients, with no serious adverse events reported (More)

NICE has recommended Galderma’s Nemluvio (nemolizumab) in patients with moderate-to-severe atopic dermatitis for NHS use in England and Wales, making it the first anti-IL-31RA biologic approved by the agency for this condition (More)

In a single-arm trial of breast cancer patients receiving anthracycline-based chemotherapy, scalp cooling was associated with an 85% lower risk of persistent chemotherapy-induced alopecia (pCIA) compared to historical controls without scalp cooling (RR 0.15; 95% CI, 0.05–0.47); pCIA is defined as hair density or thickness ≥2 standard deviations below baseline at 6 months post-chemotherapy (More)

LEO Pharma has launched the Phase 2a DELTA NEXT trial of topical pan-JAK inhibitor delgocitinib in adults with palmoplantar pustulosis, following completion of Phase 3 studies in chronic hand eczema (More)