FDA Approves Brepocitinib for Dermatomyositis

The FDA recently approved brepocitinib (Lisraya; Priovant Therapeutics) tablets for the treatment of dermatomyositis in adults. The approval makes brepocitinib the first oral treatment specifically indicated for dermatomyositis, a rare autoimmune disease in which chronic inflammation drives progressive muscle weakness and distinctive skin rashes. It is based on results from the phase 3 VALOR trial.¹

Dermatomyositis has lacked an FDA-approved targeted therapy, leaving corticosteroids and off-label immunosuppressants as the mainstay of treatment despite substantial toxicity burdens. Prior phase 3 trials of rituximab, abatacept, tocilizumab, and ustekinumab failed to meet primary end points in myositis populations. The FDA granted brepocitinib both orphan drug and priority review designations in March 2026 ahead of approval.¹

“After demonstrating high efficacy and safety in its phase 3 clinical trial data, recently published in the New England Journal of Medicine, brepocitinib now has FDA approval for the treatment of dermatomyositis. This approval ushers in a new era of targeted, non-steroidal therapy for dermatomyositis, which will mean wonders for the quality of life of patients with dermatomyositis,” said Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine and Dermatology Times’ editor in chief, in an exclusive statement.

The approval is supported by data from VALOR (NCT05437263), a randomized, double-blind, multicenter, placebo-controlled phase 3 trial conducted at 90 sites across 20 countries. Between October 2022 and June 2024, investigators enrolled 241 adults with dermatomyositis and randomized them to receive brepocitinib 30 mg once daily, brepocitinib 15 mg once daily, or placebo for a 52-week treatment period, with background therapies continued and a structured corticosteroid taper built into the protocol. More than 80% of participants had moderate to severe disease by physician global assessment, nearly 15% had a prior history of benign or malignant neoplasm, and nearly two-thirds had at least 1 cardiovascular risk factor at baseline.¹

The primary end point, mean Total Improvement Score (TIS) at week 52, was 46.5 with brepocitinib 30 mg versus 31.2 with placebo, a difference of 15.3 points (P < .001). More than two-thirds of patients receiving brepocitinib 30 mg achieved a moderate response (TIS ≥40) compared with 44% on placebo, and 46% achieved a major response (TIS ≥60) versus 26% with placebo.^1,2

Nikolay Nikolov, MD, director of the office of immunology and inflammation in the FDA's Center for Drug Evaluation and Research, said the approval addresses a longstanding gap in care. "For too long, patients with dermatomyositis have faced a significant unmet need for effective treatments, often relying on therapies meant for other diseases," Nikolov said. "Today's approval is a meaningful step forward, giving patients and their healthcare providers an approved oral therapy proven to help manage this rare and debilitating disease."¹

Ruth Ann Vleugels, MD, MPH, MBA, dermatologist and chair of dermatology at Mass General Brigham and professor of dermatology at Harvard Medical School, lead author of the VALOR trial, said the results carry broad clinical implications. "I anticipate that the VALOR trial results will be practice-changing for patients with dermatomyositis," Vleugels said. "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."¹

Safety Profile and Secondary End Points

Brepocitinib 30 mg was superior to placebo on all 9 prespecified key secondary end points, including improvements in physical function and skin disease activity, with participants more likely to reduce corticosteroid use by week 48. Skin-specific improvement occurred early, with a CDASI-A difference of -3.0 points versus placebo by week 4 (P < .001), sustained through week 52. Among patients with moderate to severe skin disease at baseline, 44% receiving brepocitinib 30 mg achieved cutaneous remission (CDASI-A ≤5) by week 52, versus 21% with placebo.^1,2

The most common adverse reactions with brepocitinib were upper respiratory tract infection, headache, fatigue, urinary tract infection, and nausea. Discontinuation due to adverse reactions occurred in 6% of participants treated with brepocitinib 30 mg, compared with 11% of those given placebo. Brepocitinib carries a boxed warning for serious infections, increased all-cause mortality, malignancies, major adverse cardiovascular events, and thrombosis, consistent with the established class profile of JAK and TYK2 inhibitors.¹

“Brepocitinib delivers dual, potent inhibition of JAK1 and TYK2, effectively reducing type I interferon signals central to the pathogenesis of dermatomyositis. Its inhibition of TYK2 is not allosteric, but orthosteric to the JH1 kinase domain, differentiating it from first- and second-generation TYK2 inhibitors for psoriasis,” Bunick said.

With FDA approval, brepocitinib becomes the first targeted therapy specifically indicated for dermatomyositis, following a string of failed phase 3 attempts with rituximab, abatacept, tocilizumab, and ustekinumab in myositis populations. For clinicians managing patients who have exhausted conventional immunosuppression or remain dependent on corticosteroids, brepocitinib offers an oral, once-daily, mechanism-guided option targeting JAK and TYK2 signaling directly.

References

1. FDA approves first oral drug indicated to treat dermatomyositis in adults. News release. US Food and Drug Administration. August 27, 2026. Accessed August 27, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-drug-indicated-treat-dermatomyositis-adults
2. JAMA Dermatology publishes skin-specific outcomes from phase 3 VALOR trial of brepocitinib in dermatomyositis. News release. Roivant Sciences. August 26, 2026. Accessed August 27, 2026. https://www.globenewswire.com/news-release/2026/08/26/3351560/34323/en/jama-dermatology-publishes-skin-specific-outcomes-from-phase-3-valor-trial-of-brepocitinib-in-dermatomyositis.html

Frequently Asked Questions

What is brepocitinib approved for?
Brepocitinib is FDA-approved for the treatment of dermatomyositis in adults, based on results from the phase 3 VALOR trial.

How does brepocitinib work?
Brepocitinib is an oral, dual TYK2/JAK1 inhibitor that suppresses signaling of type I and II interferon, IL-6, IL-12, and IL-23, cytokines implicated in dermatomyositis immunopathogenesis.

What did the VALOR trial show?
Brepocitinib 30 mg once daily produced significantly greater improvement in muscle and skin disease activity, physical function, and corticosteroid tapering compared with placebo over 52 weeks in adults with dermatomyositis.