⚡Two Firsts in SCC, Landmark Botox Trial, and Ucenprubart For AD

Good morning — it’s Saturday, June 7, and we’re covering two firsts in cutaneous squamous cell carcinoma, a landmark trial comparing botulinum toxin A formulations, and more.

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Cemiplimab (Libtayo), a PD-1 checkpoint inhibitor, took a step toward adjuvant approval in high-risk cutaneous squamous-cell carcinoma (cSCC) after demonstrating improved disease-free survival in the Phase 3 C-POST trial published in NEJM.

Investigators randomized 415 patients with local or regional high-risk cSCC—following curative surgery and radiotherapy—to cemiplimab or placebo for up to 48 weeks. High-risk features included nodal (e.g., extracapsular extension with the largest node ≥20 mm) and non-nodal criteria (e.g., in-transit metastases).

Cemiplimab significantly improved disease-free survival, defined as time to recurrence or death, compared to placebo (24 vs. 65 events; HR 0.32; P < 0.001).

At 24 months, disease-free survival was 87% in the cemiplimab group versus 64% with placebo. Additionally, more patients were estimated to remain free of locoregional (95% vs. 77%) and distant (94% vs. 84%) recurrence.

In the second part of the trial, patients who were initially on placebo and experienced recurrence could cross over to cemiplimab, with 43% achieving an objective radiographic response.

Although overall survival at 24 months was similar between groups (95% vs. 92%), follow-up is ongoing.

The safety profile was consistent with prior trials. Grade ≥3 adverse events (24% vs. 14%) and discontinuation rates (10% vs. 2%) were more frequent with cemiplimab. One treatment-related death due to myositis occurred.

While a survival benefit has yet to emerge, these findings may lead to expanded use in earlier-stage disease. Cemiplimab is already FDA-approved for unresectable or metastatic cSCC.

> First Trial of Rigosertib in EB-Associated SCC Shows Response: The first-ever cancer therapeutic trial in recessive dystrophic epidermolysis bullosa (RDEB)–associated cutaneous squamous cell carcinoma (cSCC) has shown positive early results, according to a single arm Phase 2 study in the British Journal of Dermatology. Rigosertib, originally identified as a polo-like kinase-1 (PLK1) inhibitor, disrupts multiple cancer-driving pathways, including RAS/RAF/MEK signaling. Five patients with metastatic or locally advanced cSCC unresponsive to standard care received IV or oral rigosertib. Of the four who completed more than one cycle, all showed clinical benefit: two achieved complete remission, and two had partial responses. Most side effects—such as cystitis and urinary discomfort—were manageable, with dose reductions as needed. The study supports wider exploration of rigosertib in RDEB-cSCC, the leading cause of death in this rare monogenic disease.

> Botulinum Toxin A Formulations Differ in Onset and Duration for Glabellar Strain: A landmark randomized trial published in JAMA Dermatology demonstrates differences in the efficacy of botulinum toxin A formulations for reducing glabellar strain. The study enrolled 143 women and compared four FDA-approved formulations: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), prabotulinumtoxinA (Jeuveau), and incobotulinumtoxinA (Xeomin). Using dynamic 3D photogrammetry, investigators found that Dysport and Jeuveau had the fastest onset at Day 3, reducing median glabellar strain by 67% and 62%, respectively—significantly more than Botox (48%) and Xeomin (40%). Peak efficacy was similar across all groups at Day 30. At Day 180, Jeuveau and Xeomin retained a significant effect compared to baseline, with Jeuveau showing a significantly greater effect than Botox. Despite these differences, all four formulations significantly reduced glabellar strain and improved patient satisfaction through Day 90. The authors suggest that Dysport or Jeuveau may be preferred for patients seeking rapid onset, with Jeuveau potentially offering longer-lasting results in some cases.

> Ucenprubart Shows Clinical Activity in Early Atopic Dermatitis Trial: Published in Nature Communications, the Phase 1b trial of ucenprubart—a selective CD200R agonist antibody—missed its primary endpoint in atopic dermatitis but showed signs of clinical activity. Expressed on myeloid and memory T cells, CD200R downregulates inflammation when activated. The three-part study enrolled 62 healthy volunteers (Parts A and B) and 40 patients with atopic dermatitis (Part C). At Week 12, a greater proportion of ucenprubart-treated patients achieved clear or almost clear skin (vIGA-AD 0/1) compared to placebo (32% vs. 17%), though the difference was not statistically significant (P=0.45). However, significant improvements were observed in the Eczema Area and Severity Index (EASI; –61% vs. –39%; P = 0.016). No serious adverse events, cytokine release, or treatment discontinuations occurred across all study phases. Skin biopsies suggest ucenprubart reduces dermal GATA3⁺ Th2 cells indirectly through macrophage-driven modulation of immune pathways, including NF-κB and JAK-STAT. Although limited by the small sample size, the study supports continued clinical development.

> Aclaris Advances Bosakitug Into Phase 2 Atopic Dermatitis Trial: Aclaris Therapeutics launched a randomized, double-blind, placebo-controlled Phase 2 trial of bosakitug (ATI-045), aiming to enroll 90 patients with moderate-to-severe atopic dermatitis. The decision follows encouraging results from a recently completed single-arm trial, in which 94% of patients on bosakitug experienced at least a 75% reduction in disease severity (EASI-75) at Week 26. Notably, 88% achieved clear or near-clear skin (IGA 0/1). Bosakitug is a humanized monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), a cytokine that acts as a master regulator of type 2 immune responses. By blocking TSLP, the drug may suppress downstream inflammatory mediators such as IL-4, IL-13, and CCL17. Topline results are expected in the second half of 2026

> Berotralstat Reduces Hereditary Angioedema Attacks From Childhood to Adolescence: New results from the open-label APeX-P and real-world Berolife studies highlight the efficacy of berotralstat (Orladeyo) in preventing hereditary angioedema attacks from childhood through adolescence. As a plasma kallikrein inhibitor, the drug works by reducing bradykinin generation to prevent attacks. In the APeX-P trial, children aged 2–11 receiving daily berotralstat saw a reduction in the percentage of days with angioedema symptoms from 11% to 4%, with at least half remaining attack-free each month. In the Berolife study, adolescents lowered their median monthly attack rate from 2.25 to 0.55 on treatment, with benefits sustained at 12 and 18 months. Both studies reported a safety profile consistent with earlier trials. Berotralstat is the first and only FDA-approved oral therapy to prevent hereditary angioedema attacks in patients aged 12 and older.

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

In the pooled ADORING 1 and 2 trials of 813 adults and children as young as 2 years with atopic dermatitis, tapinarof cream 1% (Vtama)—an aryl hydrocarbon receptor agonist—led to improvements in itch as early as 24 hours after first use, with significant improvement over vehicle by Day 2 (P=0.0115) (More).

In a retrospective study of 37 adults with atopic dermatitis treated with the IL-13 inhibitor tralokinumab for 1 year, 85% achieved clear or almost clear skin (IGA 0/1) at 2 months and 93% by 1 year (More)

In a double-blind, 8-week trial of 70 women with melasma and sensitive skin, 1% oxyresveratrol emulsion reduced the Modified Melasma Area and Severity Index (mMASI, range 0–24) score by 21% (vs. 6% for placebo; P < 0.05) with no reported adverse events (More)

In an observational study of 160 adults undergoing dermal filler procedures, pre-injection facial ultrasound to improve vascular visualization reduced bruising from 71% to 30% (P < 0.05) (More)

Topical roflumilast (Zoryve) becomes the first FDA-approved psoriasis treatment to earn the National Psoriasis Foundation’s Seal of Recognition for products deemed safe and non-irritating (More)

In a Danish randomized trial of 581 mother–child pairs, mothers received either high-dose (2800 IU/day) or standard-dose (400 IU/day) vitamin D during pregnancy, with no difference in the risk of development of atopic dermatitis in children by age 6 (More)

In a JAMA study of 2,066 counties across 33 U.S. states, mean county-level measles-mumps-rubella (MMR) vaccination rates fell from 94% prepandemic to 91% postpandemic (More)