Key Takeaways:
• Brepocitinib 30 mg once daily met the primary endpoint, improving the Total Improvement Score by 15.3 points versus placebo at Week 52 (P <.001); the 15 mg dose did not separate from placebo.
• Brepocitinib 30 mg was superior to placebo across all 9 key secondary endpoints, including skin disease activity, glucocorticoid tapering and physical function.
• 68% of patients on brepocitinib 30 mg reached at least moderate improvement by Week 52 versus 44% on placebo.
• Serious infections occurred more often with brepocitinib 30 mg than placebo (10% vs 1%), though no deaths were reported.
• An open-label extension is ongoing to characterize longer-term use of brepocitinib.
Brepocitinib, a first-in-class oral TYK2-JAK1 inhibitor, achieved a significantly greater improvement in disease activity than placebo at Week 52 in a phase 3 trial of adults with treatment-refractory dermatomyositis, according to data resulting from the VALOR trial and published in the New England Journal of Medicine.¹
Dermatomyositis has lacked an approved oral targeted therapy, with glucocorticoids, conventional DMARDs and intravenous immune globulin associated with incomplete efficacy and considerable toxicity.
Brepocitinib blocks TYK2 and JAK1 signaling implicated in the type I and II interferon and interleukin-driven inflammation of dermatomyositis, offering a mechanism distinct from broader JAK inhibition.²
Brepocitinib VALOR Trial Design and Primary Endpoint
The phase 3 VALOR trial (NCT05437263) randomized 241 adults with treatment-refractory dermatomyositis 1:1:1 to once-daily oral brepocitinib 30 mg, brepocitinib 15 mg or placebo for 52 weeks across 90 sites in 20 countries. Patients continued standard background therapy, and glucocorticoids were tapered per protocol starting at Week 12.
The mean patient age was 50.6 years, and 77.6% were women. Nearly all patients (92.9%) were receiving at least 1 dermatomyositis-directed systemic therapy at baseline, and most (81.3%) had moderate to severe disease activity.
The primary endpoint was the Total Improvement Score, a composite myositis index ranging from 0 - 100, at Week 52. Brepocitinib 30 mg produced a mean score of 46.5 versus 31.2 with placebo, a least-squares mean difference of 15.3 points (95% CI, 6.7-24.0; P <.001). The 15 mg dose did not separate from placebo (mean score, 37.5; difference, 6.3; 95% CI, -2.4-14.9), and no further hypothesis testing was performed for the 15 mg dose.
Brepocitinib Secondary Endpoints and Safety Profile
Brepocitinib 30 mg was superior to placebo across all 9 prespecified secondary endpoints. A moderate improvement (Total Improvement Score ≥40) was reached by 68% of patients versus 44% on placebo (risk difference, 22.2 percentage points; 95% CI, 7.1-37.3; P = .004), and a major improvement (score ≥60) by 46% versus 26% (risk difference, 19.5 percentage points; 95% CI, 4.2-34.8; P = .01).
Skin disease activity, measured by the Cutaneous Dermatomyositis Disease Area and Severity Index-Activity, improved by a least-squares mean of 6.4 points at Week 4 with brepocitinib 30 mg versus 3.5 points with placebo (difference, -3.0; 95% CI, -4.6 to -1.4; P <.001). By Weeks 48 to 52, 62% of brepocitinib 30 mg patients on baseline glucocorticoids tapered to 2.5 mg or less of prednisone equivalent daily versus 34% on placebo, and 42% reached 0 mg versus 23% on placebo.
Adverse events occurred at similar rates across groups (90% with brepocitinib 30 mg, 86% with 15 mg and 91% with placebo). Serious infections were more frequent with brepocitinib 30 mg than with the 15 mg dose or placebo (10% vs 2% vs 1%), though these events resolved with medical management and most patients completed treatment.
Adverse events of special interest were uncommon and occurred at similar frequencies across groups. Thromboembolic events and new or recurrent cancers occurred only in the placebo group, and no deaths were reported during the trial.
Priovant Therapeutics, which funded the trial, is continuing to evaluate brepocitinib in an ongoing 52-week open-label extension designed to characterize its use under more flexible background-therapy conditions.
References
Vleugels RA, Paik JJ, Bauer Ventura I, et al. A phase 3 trial of brepocitinib in dermatomyositis. N Engl J Med. 2026;394(19):1883-1893. doi:10.1056/NEJMoa2503531.
ClinicalTrials.gov. Study to investigate the efficacy and safety of brepocitinib in adults with dermatomyositis (VALOR). NCT05437263. Accessed August 8, 2026.
