⚡First-in-Class Treg Therapy for Eczema

Good morning — it’s Saturday, July 5, and we’re covering a potential first-in-class Treg stimulator for atopic dermatitis, new trial results for a single-application gene therapy for EB published in The Lancet, and more.

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Nektar Therapeutics announced that rezpegaldesleukin (Rezpeg) met primary and key secondary endpoints in the Phase 2b REZOLVE-AD trial for moderate-to-severe atopic dermatitis.

Rezpeg is a regulatory T cell (Treg)-selective IL-2 receptor agonist that expands CD25⁺ Tregs—critical for immune tolerance—and spares conventional T cells. This approach aims to restore immune balance in inflammatory diseases.

The global trial enrolled 393 patients randomized to three Rezpeg dosing regimens or placebo.

At Week 16, 42–46% of patients receiving the higher doses reached at least a 75% reduction in disease severity (EASI 75), compared to 17% on placebo (P < 0.001). Clear or near-clear skin (vIGA-AD 0/1) was achieved by 20–26% versus 8% on placebo.

Blood biomarker analyses supported the drug’s mechanism, showing increased circulating Tregs and reduced Th2-associated markers such as TARC/CCL17 and MDC/CCL22.

Most adverse events were mild to moderate. Injection site reactions occurred in 70% of treated patients, though they were typically transient. Other common side effects (>5%) included eosinophilia, pyrexia, headache, and arthralgia.

Rezpeg is also being studied in alopecia areata, with top-line results expected in Q4 2025.

> Zevaskyn improves wound healing and pain in RDEB after single-gene therapy application: Prademagene zamikeracel (Zevaskyn) significantly improved wound healing and pain in recessive dystrophic epidermolysis bullosa (RDEB), according to Phase 3 results from the VIITAL trial published in The Lancet. Zevaskyn is a one-time gene therapy delivered via surgical grafting of autologous keratinocyte sheets genetically corrected for COL7A1, the gene mutated in RDEB. Investigators randomized 86 large, chronic wounds across 11 patients. By Week 24, 81% of Zevaskyn-treated wounds achieved ≥50% healing compared to 16% of matched control wounds (P < 0.0001). Patients also reported greater reductions in pain (–3.1 vs –0.9 points on a 0–10 scale; P = 0.0002). Safety data were favorable, with only mild adverse events reported. Limitations include the small sample size, lack of blinding, and enrollment restricted to patients expressing the NC1 portion of type VII collagen, potentially limiting generalizability. The findings build on earlier Phase 1/2a data showing durable healing after two years. Zevaskyn distinguishes itself from beremagene geperpavec (Vyjuvek) and birch bark triterpenes (Filsuvez) by avoiding the need for ongoing application. Priced at $3.1 million per treatment, it received FDA approval earlier this year.

> Flex Up trial explores response-guided dosing of upadacitinib in atopic dermatitis: The Phase 3b/4 Flex Up trial evaluated response-guided dosing of upadacitinib (Rinvoq) in moderate-to-severe atopic dermatitis, as reported in the British Journal of Dermatology. A total of 461 adults were randomized to once-daily upadacitinib 15 mg or 30 mg. At Week 12, responders either continued or stepped down their dose, while nonresponders escalated or remained on their starting dose. By Week 24, EASI 90—defined as ≥90% improvement in eczema severity—was achieved by 48% of patients who escalated from 15 to 30 mg and maintained by 69% who de-escalated from 30 to 15 mg. Response rates were 75% among patients who responded and remained on 15 mg, and 29% among those who did not respond and continued on 30 mg. Treatment-emergent adverse events occurred in 43% of patients who remained on 15 mg, 54% who escalated from 15 mg to 30 mg, 62% who continued on 30 mg, and 49% who de-escalated from 30 mg to 15 mg. No malignancies, venous thromboembolic events, or deaths were reported. Adverse events ≥5% included nasopharyngitis, acne, oral herpes, and eczema. The findings may help guide personalized dosing decisions in practice.

> Three-Year Data Show Durable Joint and Skin Responses With Bimekizumab in Psoriatic Arthritis: Three-year results show that bimekizumab (Bimzelx) maintains deep, sustained improvements in joint and skin outcomes in psoriatic arthritis. The data, presented by UCB at EULAR 2025, come from the Phase 3 BE OPTIMAL and BE COMPLETE trials and their open-label extension, BE VITAL. Investigators enrolled both biologic-naïve patients and those with an inadequate response to TNF inhibitors (TNFi-IR). At Year 3, 53% of biologic-naïve and 55% of TNFi-IR patients achieved the stringent ACR50 endpoint—defined as at least 50% improvement in tender and swollen joint counts and in at least three of five additional domains. Complete skin clearance (PASI 100) was maintained in 62% and 68% of biologic-naïve and TNFi-IR patients, respectively. Safety outcomes remained favorable, with few patients discontinuing therapy due to Candida infections. Bimekizumab remains the only approved therapy that selectively targets both IL-17A and IL-17F.

> Guselkumab clears scalp psoriasis across all skin tones in VISIBLE trial: Guselkumab (Tremfya) achieved high clearance rates in adults with moderate to severe scalp psoriasis and skin of color, according to the Phase 3b VISIBLE trial published in JAMA Dermatology. Investigators randomized 108 participants to guselkumab or placebo, with crossover at Week 16. Over 60% had Fitzpatrick skin types IV–VI, and the mean Dermatology Life Quality Index (DLQI) score was 14 (range 0–30), indicating a moderate to severe impact on quality of life. At Week 16, 68% of guselkumab-treated patients achieved absent or very mild scalp psoriasis (ss-IGA 0/1) versus 12% on placebo. Efficacy continued to improve, with ~80% reaching this outcome by Week 48. Additionally, more than 60% reported no impact on quality of life (DLQI scores of 0 or 1). Safety was in line with previous trials. The results challenge body surface area–based treatment thresholds and suggest that systemic therapy be considered for high-impact sites like the scalp across diverse skin tones.

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

A retrospective real-world study of 28 patients with atopic dermatitis unresponsive to upadacitinib found that 60% achieved ≥75% reduction in disease severity (EASI 75) after switching to the IL-13 inhibitor lebrikizumab (More)

La Roche-Posay’s Mela B3® serum (MB3; 0.5% 2-mercaptonicotinoyl glycine) was shown to be non-inferior to hydroquinone 4% in a 3-month single-blind randomized trial of 109 women with facial melasma, reducing the Modified Melasma Area and Severity Index by 29% versus 34%. It also caused fewer local skin reactions at 1 month (6% vs. 21%) (More)

In a multicenter study of 418 patients with recently healed diabetic foot ulcers, wound recurrence by 16 weeks occurred in 35% of those with high baseline transepidermal water loss measured at the center of the closed wound, compared to 17% with low levels (OR 2.66; 95% CI, 1.57–4.49) (More)

In a Phase 3 trial of 300 participants with moderate-to-severe glabellar lines, 81% of those receiving CKDB-501A—a botulinum toxin formulation free from animal-derived components—achieved a ≥2-point improvement on the Facial Wrinkle Scale (range 0–3) by Week 4, compared to 71% of those receiving onabotulinumtoxinA (Botox) (P = 0.049) (More)

In a retrospective study of 32 patients with 51 hyperkeratotic actinic keratoses, tirbanibulin 1% ointment achieved complete clearance in 55% of lesions and partial clearance in 26% (defined as >75% reduction) at 8 weeks, with no severe local skin reactions reported; the agent inhibits tubulin polymerization and has potent antiproliferative and antitumor activity (More)