Lisraya (brepocitinib): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat dermatomyositis in adultsWording from FDA's list of novel approvals.
FDA review
Priority reviewOrphan drug
Company
Priovant Therapeutics
Application
NDA 220106
Specialty
Dermatology
Boxed warning: Serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis
At a glance
Lisraya is the first oral drug approved for adult dermatomyositis and the first TYK2/JAK1 inhibitor on the market. In the 52-week phase 3 VALOR trial, added to standard therapy, it raised the Total Improvement Score by 15 points over placebo and beat placebo on every key secondary end point, including skin activity and steroid tapering. It carries the JAK-class boxed warning.
What it is and how it works
Brepocitinib blocks two intracellular kinases, TYK2 and JAK1, more strongly than JAK2 or JAK3. That cuts signaling from type I interferon, which drives much of the muscle and skin inflammation in dermatomyositis, and from cytokines such as interleukin-6. It is taken by mouth.
Phase 3, randomized (1:1:1), double-blind, placebo-controlled, 52 weeks. Two doses were compared with placebo; standard therapies continued and glucocorticoids were tapered.
Patients
241 adults with dermatomyositis active despite earlier therapy; 78% women, mean age 51; 76% on oral glucocorticoids and 72% on another immunosuppressant at baseline.
Compared with
Placebo, on top of standard therapy.
Primary endpoint
Mean Total Improvement Score at week 52 (a composite myositis index from 0 to 100; higher is better).
Result
Mean score 46.5 with the approved dose versus 31.2 with placebo: a difference of 15.3 points (95% CI, 6.7 to 24.0; P<0.001). The lower dose, which FDA did not approve, did not differ significantly from placebo (6.3 points; 95% CI, -2.4 to 14.9).
Other results
The approved dose beat placebo on all nine key secondary end points in the multiplicity-controlled sequence, including skin disease activity, glucocorticoid tapering and physical function, with separation from week 4.
Safety in the trial
Serious infections 10% versus 1% with placebo; no deaths.
How does Lisraya (brepocitinib) compare with the alternatives (Intravenous immunoglobulin (IVIG), Glucocorticoids, Methotrexate, mycophenolate or azathioprine) for dermatomyositis in adults? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Safety signals
The label carries the boxed warning shared by JAK inhibitors: serious infections, death, malignancy, major adverse cardiovascular events and thrombosis. In VALOR, serious infections occurred in 10% of patients on the approved dose versus 1% on placebo; there were no deaths. Before starting, the label calls for tuberculosis and viral hepatitis screening, blood counts, liver and kidney tests and up-to-date vaccines. It should not be combined with other JAK or TYK2 inhibitors or biologic DMARDs, and the label notes that smoking lowers brepocitinib exposure and may reduce its effect. In the trial, 65% of patients had a cardiovascular risk factor or atherosclerotic disease and 20% had interstitial lung disease.
What it competes with
Dermatomyositis is usually treated with glucocorticoids plus a steroid-sparing drug, and intravenous immunoglobulin (IVIG) was until now the only FDA-approved therapy for adults. Lisraya was tested on top of these background treatments in patients still active despite them.
Intravenous immunoglobulin (IVIG)The other FDA-approved therapy for adult dermatomyositis; given by infusion.
Methotrexate, mycophenolate or azathioprineUsual steroid-sparing drugs, continued as background therapy in VALOR.
RituximabUsed off-label for refractory disease.
Other JAK inhibitorsUsed off-label; the label says not to combine them with Lisraya.
Bottom line for clinicians
For adults whose dermatomyositis stays active on standard therapy, Lisraya adds an approved oral option with a clinically meaningful gain at one year and help with steroid tapering. Screen for infection before starting and weigh the boxed warning, especially in older patients and those with cardiovascular risk factors.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 27, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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