Brepocitinib Improves Skin Disease Activity in Dermatomyositis

Brepocitinib, an oral TYK2 and JAK1 inhibitor in development by Priovant Therapeutics, produced rapid and durable improvements in skin disease activity, itch, and quality of life in adults with dermatomyositis, according to a secondary analysis of the phase 3 VALOR trial published in JAMA Dermatology. At week 52, 61.7% of patients receiving brepocitinib 30 mg (50/81) achieved a clinically meaningful response on the Cutaneous Dermatomyositis Disease Area and Severity Index-Activity (CDASI-A), compared with 44.3% receiving placebo (35/79). Clinically meaningful response was defined as a 40% or greater relative and 4-point or greater absolute improvement from baseline. The findings build on primary VALOR results previously reported in the New England Journal of Medicine, in which brepocitinib 30 mg demonstrated superiority over placebo on the trial's primary myositis end point.²

Cutaneous involvement in dermatomyositis has historically been difficult to control, with patients often experiencing gradual or incomplete improvement despite systemic corticosteroids, conventional immunosuppressants, and intravenous immunoglobulin. The VALOR secondary analysis evaluated the effects of targeted TYK2/JAK1 inhibition on skin disease activity, itch, skin-related quality of life, and remission-level outcomes over 52 weeks of treatment.¹

VALOR (NCT05437263) randomized 241 adults with dermatomyositis 1:1:1 to once-daily oral brepocitinib 30 mg, brepocitinib 15 mg, or placebo across 90 sites in 20 countries between October 2022 and July 2025. Participants had active skin and muscle disease at enrollment. Because only the 30-mg dose demonstrated superiority over placebo on the primary efficacy end point, the skin-specific analysis focused primarily on comparisons between brepocitinib 30 mg and placebo.^1,4

Beginning at week 4, brepocitinib 30 mg demonstrated greater reductions from baseline in CDASI-A score compared with placebo (-6.4 vs -3.5; difference, -3.0; 95% CI, -4.6 to -1.4; P < .001). Among participants with moderate to severe skin disease at baseline, 45.7% receiving brepocitinib 30 mg (21/46) achieved a Cutaneous Dermatomyositis Activity-Investigator's Global Assessment (CDA-IGA) score of clear or almost clear with at least a 2-point improvement by week 52, compared with 21.8% receiving placebo (12/55; difference, 21.1 percentage points; 95% CI, 2.5-39.7). Among participants with a baseline CDASI-A score greater than 14, functional skin remission, defined as a CDASI-A score of 5 or lower, was achieved by 43.5% of patients receiving brepocitinib (20/46) compared with 20.8% receiving placebo (11/53; difference, 26.6 percentage points; 95% CI, 7.6-45.5).¹

Brepocitinib Safety Profile and Secondary End Points in Dermatomyositis

Itch also improved rapidly with brepocitinib 30 mg. Among patients with at least moderate itch at baseline, 54.0% (27/50) achieved a 2-point or greater reduction in Peak Pruritus-Numerical Rating Scale (PP-NRS) score by week 4, compared with 9.5% receiving placebo (4/42; difference, 47.3 percentage points; 95% CI, 30.4-64.1). By week 52, response rates increased to 74.0% (37/50) and 33.3% (14/42), respectively.¹

Skin-related quality of life, measured using Skindex-16, improved by a mean of 12.9 points from baseline with brepocitinib 30 mg at week 4 compared with 0.9 points with placebo, with the brepocitinib group exceeding the instrument's 10-point minimal clinically important difference. Among patients receiving oral corticosteroids at baseline, 61.7% receiving brepocitinib 30 mg (37/60) tapered to a prednisone-equivalent dose of 2.5 mg/d or less by week 52, compared with 34.4% receiving placebo (22/64). Additionally, 41.7% (25/60) discontinued oral corticosteroids entirely compared with 23.4% receiving placebo (15/64).¹

Adverse events occurred at similar rates with brepocitinib 30 mg and placebo (90.1% vs 91.1%, respectively). Serious infections occurred more frequently with brepocitinib 30 mg than placebo (9.9% [8/81] vs 1.3% [1/79]); most were respiratory infections and resolved with standard medical management, with treatment reinitiated in most patients. Malignant neoplasms, cardiovascular events, and thromboembolic events were observed more often in the placebo group. No deaths were reported.¹

Victoria P. Werth, MD, professor of dermatology and medicine at the Perelman School of Medicine at the University of Pennsylvania and a VALOR investigator, noted the substantial quality-of-life burden associated with cutaneous dermatomyositis. In a company announcement accompanying publication of the analysis, Werth described the sustained improvements in disease activity and itch, along with remission-level outcomes among patients with more severe skin disease, as "a monumental finding for patients with dermatomyositis."³

Brepocitinib is also in late-stage clinical development for noninfectious uveitis, cutaneous sarcoidosis, and lichen planopilaris. The drug is not currently FDA approved. In March 2026, the FDA accepted Priovant's New Drug Application for brepocitinib in dermatomyositis and granted Priority Review, with a Prescription Drug User Fee Act target action date in the third quarter of 2026.⁴

References

1. Mangold AR, Haemel A, Shahriari N, et al. Skin-specific outcomes of brepocitinib in patients with dermatomyositis: secondary analysis of a phase 3 randomized clinical trial. JAMA Dermatol. Published online August 26, 2026. doi:10.1001/jamadermatol.2026.3199
2. Vleugels RA, Paik JJ, Bauer Ventura I, et al; VALOR Investigators. A phase 3 trial of brepocitinib in dermatomyositis. N Engl J Med. 2026;394(19):1883-1893. https://pubmed.ncbi.nlm.nih.gov/41910335/
3. JAMA Dermatology publishes skin-specific outcomes from phase 3 VALOR trial of brepocitinib in dermatomyositis. Roivant Sciences. Published August 26, 2026. Accessed August 28, 2026. https://investor.roivant.com/news-releases/news-release-details/jama-dermatology-publishes-skin-specific-outcomes-phase-3-valor
4. Priovant announces FDA acceptance and Priority Review of New Drug Application for brepocitinib in dermatomyositis. Roivant Sciences. Published March 3, 2026. Accessed August 28, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-drug-indicated-treat-dermatomyositis-adults