Brepocitinib for dermatomyositis is now FDA approved as Lisraya, an oral Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) inhibitor and the first FDA-approved oral drug specifically indicated for adults with the disease on August 27, 2026, after the phase 3 VALOR trial published in The New England Journal of Medicine showed significant improvement in a validated composite measure of muscle, skin, and overall disease activity. The randomized, double-blind study enrolled 241 adults with active dermatomyositis and compared brepocitinib 30 mg once daily, brepocitinib 15 mg once daily, and placebo for 52 weeks while standard background therapies were continued and glucocorticoids were tapered.
Dermatomyositis affects muscle and skin and has long relied on off-label treatment
Dermatomyositis is a rare systemic autoimmune disease characterized by inflammatory muscle weakness and distinctive skin disease. It can also involve the lungs and other organs. The condition belongs to the broader group of idiopathic inflammatory myopathies and can cause substantial disability when inflammation remains active.
Until Lisraya, treatment frequently relied on glucocorticoids and immunomodulatory drugs used outside a dermatomyositis-specific oral FDA indication. That history reflects a broader pattern of drug repurposing and off-label treatment in diseases with limited approved options. Dermatomyositis is also part of the wider autoimmune-disease landscape, where dysregulated immune signaling drives tissue injury, as seen in conditions such as lupus and multiple sclerosis.
FDA described the approval as the first oral treatment option specifically approved for dermatomyositis in adults. Nikolay Nikolov, M.D., director of the Office of Immunology and Inflammation at FDA, said the approval was “a meaningful step forward” for patients with the disease.
Brepocitinib for dermatomyositis was tested in the 52-week VALOR trial
VALOR, also identified as NCT05437263, randomly assigned 241 adults in a 1:1:1 ratio to brepocitinib 30 mg once daily, brepocitinib 15 mg once daily, or placebo. There were 81 participants in each brepocitinib group and 79 in the placebo group. Standard dermatomyositis therapies could be continued, and the protocol included glucocorticoid tapering.
The study population was 78% female and 72% White, with a mean age of 51 years in the FDA review. At baseline, 76% were taking oral corticosteroids, 72% were receiving a nonsteroid immunosuppressive therapy, and 27% were using antimalarial therapy.
The primary endpoint was the Total Improvement Score (TIS) at week 52. TIS is a validated composite index that integrates physician and patient global assessments, manual muscle testing, extramuscular disease activity, physical function, and muscle-enzyme measurements. Scores range from 0 to 100, with higher scores indicating greater improvement.
The approved 30 mg dose improved the primary endpoint and multiple secondary measures
In the peer-reviewed VALOR publication, mean TIS at week 52 was 46.5 with brepocitinib 30 mg, 37.5 with brepocitinib 15 mg, and 31.2 with placebo. The difference between 30 mg and placebo was 15.3 points (95% confidence interval, 6.7 to 24.0; P<0.001). The 15 mg dose did not significantly outperform placebo on the primary endpoint.
The final FDA prescribing information reports least-squares mean TIS values of 47.5 with Lisraya 30 mg and 33.3 with placebo, a difference of 14.2 points (95% confidence interval, 5.5 to 22.9). The label also reports that 48% of patients receiving Lisraya achieved major improvement, defined as TIS of at least 60, compared with 26% of placebo recipients.
The benefit extended beyond the composite score. FDA reported improvement in individual physician and patient assessments, manual muscle testing, physical function, and skin disease activity. Among patients receiving corticosteroids, 55% of Lisraya-treated patients achieved at least moderate improvement together with a corticosteroid dose of 2.5 mg per day or less at week 52, compared with 30% receiving placebo.
The VALOR investigators concluded that the 30 mg dose “resulted in significant benefits” across the composite myositis index, skin disease, glucocorticoid tapering, and functional disability.
Brepocitinib blocks cytokine signaling through TYK2 and JAK1
Brepocitinib inhibits Janus kinase (JAK) and tyrosine kinase 2 (TYK2) signaling, with greater inhibitory potency against TYK2 and JAK1 than JAK2 or JAK3 in cell-free assays. These kinases transmit signals from cytokine receptors to signal transducer and activator of transcription (STAT) proteins, which then alter gene expression and immune-cell behavior.
In blood cells from patients with dermatomyositis, brepocitinib inhibited type I interferon and interleukin-6 signaling. FDA notes, however, that the contribution of inhibition of specific JAK combinations to clinical effectiveness is not known. The mechanism therefore fits the inflammatory biology of dermatomyositis without proving that one cytokine pathway alone explains the clinical response.
The approval adds another targeted treatment to a growing group of therapies for rare diseases with historically limited treatment options, although Lisraya acts through immune signaling rather than by correcting a genetic defect.
The safety profile includes the class boxed warning carried by JAK inhibitors
Lisraya carries a boxed warning for serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. The label instructs clinicians to test for tuberculosis before treatment, monitor for infections, and consider cardiovascular, malignancy, and thrombotic risk when deciding whether to use the drug.
In VALOR, serious infections occurred in 10% of patients receiving brepocitinib 30 mg and 1% receiving placebo in the published trial. No deaths occurred during the 52-week randomized study.
In the FDA label, adverse reactions reported in at least 5% of Lisraya-treated patients and at least 2 percentage points more often than placebo included upper respiratory tract infection, headache, fatigue, urinary tract infection, nausea, bronchitis, arthralgia, diarrhea, back pain, falls, influenza, and acne.
The approval is specific to the 30 mg once-daily dose
The FDA-approved dose is 30 mg by mouth once daily, with or without food. The 15 mg dose studied in VALOR is not an approved dosage. The label also advises against combining Lisraya with other JAK inhibitors, other TYK2 inhibitors, or biologic disease-modifying antirheumatic drugs.
Before treatment, FDA recommends evaluation for tuberculosis, viral hepatitis, blood-count abnormalities, liver function, pregnancy status, and immunization status. Live vaccines should be avoided during treatment.
What the evidence cannot yet answer
VALOR establishes efficacy over 52 weeks in adults with active dermatomyositis, but it does not establish long-term comparative effectiveness against every immunosuppressive regimen used in practice. The trial also does not determine how well the results generalize to patients who would have been excluded because of specific comorbidities or laboratory abnormalities.
The trial was funded by Priovant Therapeutics, the company that developed Lisraya. The published study included company-affiliated authors and disclosed investigator relationships with industry. That sponsorship does not negate the randomized, placebo-controlled findings, but it remains relevant context for interpretation and for the importance of post-approval effectiveness and safety data.
Longer follow-up will also be important because the boxed warnings for JAK inhibitors concern uncommon but clinically serious events that may not be fully characterized by a 241-patient trial.
FDA approval converts a phase 3 signal into the first oral dermatomyositis indication
The 30 mg dose succeeded where the lower dose did not: it improved the primary composite endpoint and a broad set of muscle, skin, functional, and steroid-sparing outcomes. FDA’s approval therefore establishes brepocitinib as the first oral therapy specifically indicated for adults with dermatomyositis, while the drug’s JAK-inhibitor safety profile makes careful patient selection and monitoring essential.
References
- Vleugels RA, Paik JJ, Bauer Ventura I, et al. A Phase 3 Trial of Brepocitinib in Dermatomyositis. N Engl J Med. 2026;394:1883-1893. DOI: 10.1056/NEJMoa2503531.
- U.S. Food and Drug Administration. FDA Approves First Oral Drug Indicated to Treat Dermatomyositis in Adults. August 27, 2026. FDA press release.