VALOR: Brepocitinib AAD Data Support Priority Review for Dermatomyositis

Brepocitinib, an investigational oral therapy targeting TYK2 and JAK1 produced rapid, sustained improvements in global disease activity, skin disease, itch, and physical function in adults with dermatomyositis who had failed multiple prior treatments, prompting the United States Food and Drug Administration (US FDA) to grant the therapy Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date in the third quarter of 2026.1,2,3

The new data, from the phase 3 VALOR trial, were published March 28 in the New England Journal of Medicine and simultaneously presented as a late-breaking abstract at the 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31.1,2

Brepocitinib 30 mg (Priovant Therapeutics) achieved a statistically significant 15.3-point greater improvement in mean Total Improvement Score at week 52 compared with placebo — meeting the primary endpoint and all nine key secondary endpoints — while enabling nearly twice as many patients to meaningfully reduce background corticosteroid use, findings that position the drug as potentially the first targeted therapy approved for the disease.¹

Background and Mechanism

Dermatomyositis is a rare systemic autoimmune disease characterized by proximal muscle weakness, recalcitrant cutaneous eruptions, disabling pruritus, and risks of interstitial lung disease and malignancy. Current standard-of-care relies on systemic glucocorticoids, immunosuppressants, and intravenous immunoglobulin — agents with limited efficacy, significant toxicity, and no targeted mechanism specific to dermatomyositis pathogenesis. Most patients require multiple therapies, often achieving only partial disease control while accumulating steroid-related morbidity.¹

Brepocitinib is a first-in-class oral selective inhibitor of TYK2 and JAK1. This dual-targeting profile suppresses type I and type II interferon signaling, IL-6, IL-12, and IL-23, all cytokine pathways implicated in dermatomyositis pathogenesis.⁴ Preclinical work demonstrated that type I interferon drives myotube damage and dermal microvascular injury in dermatomyositis, both of which were attenuated by brepocitinib at clinically relevant concentrations — providing the mechanistic rationale for the VALOR trial.⁴

VALOR Trial Design

VALOR (NCT05437263) was a phase 3, randomized, double-blind, placebo-controlled trial enrolling 241 adults with definite or probable dermatomyositis across 90 global sites. Patients were randomized 1:1:1 to brepocitinib 30 mg once daily, brepocitinib 15 mg once daily, or placebo for 52 weeks. Stable background therapy with a single antimalarial agent, a single DMARD, or both was permitted. Patients on glucocorticoids at baseline tapered to ≤20 mg prednisone-equivalent before randomization, with further protocol-guided tapering from weeks 12 to 36.¹

The population was heavily pretreated and refractory: mean age was 50.6 years, 77.6% were women, 81.3% had moderate-to-severe disease activity at baseline, and approximately 2/3 were receiving 2 or more background agents at enrollment.¹ The primary endpoint was mean Total Improvement Score (TIS) at week 52 — a validated composite myositis index scored 0 to 100, with higher scores reflecting greater clinical improvement across six core measures of disease activity.¹

Late Breaking Data

Brepocitinib 30 mg met the primary endpoint with a mean TIS of 46.5 at week 52 versus 31.2 with placebo, a least-squares mean difference of 15.3 points (95% CI, 6.7–24.0; P <.001).¹ The 15 mg dose achieved a mean TIS of 37.5 — a 6.3-point difference versus placebo that did not reach statistical significance.¹

Treatment effects with brepocitinib 30 mg were evident as early as week 4 and sustained at every visit through week 52. More than 2/3 of patients in the 30 mg arm achieved TIS ≥40, twice the minimum clinically important difference; more than half achieved TIS ≥40 while simultaneously reducing corticosteroid use to ≤2.5 mg/day prednisone-equivalent — a composite outcome reflecting both disease control and meaningful steroid-sparing benefit.²,³ Brepocitinib 30 mg also demonstrated statistically significant improvements on all nine key secondary endpoints, including muscle strength, CDASI-A skin disease activity, functional disability, and corticosteroid tapering, with nearly twice as many patients reducing background corticosteroids compared with placebo.¹,²,³

The AAD late-breaking presentation by Ruth Ann Vleugels, MD, MBA, MPH, of Mass General Brigham and Harvard Medical School, extended the VALOR dataset with skin-specific and patient-reported outcomes not fully captured in the NEJM publication.²

Among patients with a baseline pruritus numeric rating scale (PP-NRS) score of ≥4, 54.0% achieved a ≥2-point improvement in itch at week 4 with brepocitinib 30 mg versus 9.5% with placebo. An 18.9% greater proportion achieved itch remission (PP-NRS ≤1) at week 4 (95% CI: 5.0–32.9), with benefits sustained through week 52.²

Skin-related quality of life, assessed by Skindex-16, showed a mean change of −12.9 in the brepocitinib 30 mg arm versus −0.9 with placebo at week 4, with continued improvements sustained across the trial.² Among the 64% of patients with moderate-to-severe skin disease at baseline — a population particularly refractory to existing therapies — brepocitinib 30 mg was associated with a 26.6% higher rate of functional skin remission by CDASI-A compared with placebo (95% CI: 7.6–45.5; P =.0060), and a 23.9% higher rate of Cutaneous Dermatomyositis Investigator Global Assessment "Clear" or "Almost Clear" status with ≥2-grade improvement (45.7% vs 21.8%).²

Safety

Serious infections occurred more frequently with brepocitinib 30 mg than with placebo (10% vs 1%), the most clinically meaningful safety signal in the trial. These events resolved with medical management and treatment was completed in most cases.¹ Adverse events leading to discontinuation occurred more frequently in the placebo arm, as did malignancies, cardiovascular events, and thromboembolic events — findings the NEJM authors attribute to the elevated baseline disease burden and chronic immunosuppressive treatment carried by the placebo population rather than a protective drug effect.¹ The overall brepocitinib safety profile across more than 2,000 patients in the clinical development program was characterized as consistent with approved JAK and TYK2 inhibitors.³

Clinical Significance

"I anticipate that the VALOR trial results… will be practice-changing for patients with dermatomyositis," Vleugels said in a statement.3 "These findings underscore the need to move beyond the historical paradigm of suboptimal disease control and reliance on systemic corticosteroids toward a patient-centric model focused on rapid, sustained, steroid-sparing efficacy with a modern, targeted therapy."³

If approved, brepocitinib would be the first targeted therapy specifically approved for dermatomyositis, addressing a disease where the clinical trial landscape has been marked by repeated failures of immunosuppressants and biologic agents.

References

1. Vleugels RA, Paik JJ, Bauer Ventura I, et al. A phase 3 trial of brepocitinib in dermatomyositis. N Engl J Med. Published March 28, 2026. doi:10.1056/NEJMoa2503531

2. Vleugels RA. Brepocitinib achieves rapid and sustained control of cutaneous disease activity, itch, and skin-related quality of life in dermatomyositis: results from the phase 3 VALOR trial. Late-breaking abstract 78745 presented at: 2026 American Academy of Dermatology Annual Meeting; March 27–31, 2026; Denver, CO.

3. Priovant Therapeutics. New England Journal of Medicine publishes positive phase 3 VALOR trial results of brepocitinib in dermatomyositis. News release. March 28, 2026. https://www.globenewswire.com/news-release/2026/03/28/3264202/34323/en/New-England-Journal-of-Medicine-Publishes-Positive-Phase-3-VALOR-Trial-Results-of-Brepocitinib-in-Dermatomyositis.html

4. Paik JJ, Vencovský J, Charles-Schoeman C, et al. Brepocitinib, a potent and selective TYK2/JAK1 inhibitor: scientific and clinical rationale for dermatomyositis. Clin Exp Rheumatol. 2025;43(2):354–363. doi:10.55563/clinexprheumatol/eeglsa