Brepocitinib clears skin in 69% with cutaneous sarcoidosis

In the randomized phase 2 BEACON trial, 69.2% of adults with cutaneous sarcoidosis receiving brepocitinib 45 mg once daily achieved clear or almost-clear skin at week 16, versus 0% receiving placebo. The JAMA Dermatology report, published online November 10, 2026, tested the oral selective tyrosine kinase 2/Janus kinase 1 inhibitor in an inflammatory disease with no FDA-approved therapy.

Cutaneous sarcoidosis is a granulomatous inflammatory disease that can leave permanent scarring, dyspigmentation, cicatricial alopecia and facial disfigurement. Lupus pernio and chronic plaque-type disease can be especially difficult to treat.

Care relies largely on off-label antimalarials, immunosuppressants, tumor necrosis factor inhibitors, and systemic or topical glucocorticoids. Sustained control remains difficult, and prolonged treatment can produce cumulative adverse effects.

Misha Rosenbach, MD, professor of dermatology and rheumatology and director of the Cutaneous Sarcoidosis Program at the Hospital of the University of Pennsylvania, said in a Priovant Therapeutics release: “Cutaneous sarcoidosis is often on the face and severely impacts patients, and there are no approved treatments.”

What did BEACON test?

BEACON’s randomized, double-blind, placebo-controlled phase 2 segment enrolled 31 adults with biopsy-confirmed active cutaneous sarcoidosis across 18 US clinical sites. Treatment lasted 16 weeks.

• Brepocitinib 45 mg once daily: 13 patients
• Brepocitinib 15 mg once daily: 11 patients
• Placebo: 7 patients

The primary endpoint measured the change from baseline in the Cutaneous Sarcoidosis Activity and Morphology Instrument–Activity score at week 16. CSAMI-A is a validated measure of inflammatory skin-disease activity.

Participants had longstanding disease, with a mean duration of 8.1 years and a baseline CSAMI-A score of 33.6. Approximately 74% were Black, and 58% had extracutaneous organ involvement. Patients taking oral glucocorticoids at baseline underwent a mandatory taper, with complete discontinuation required by week 8.

How strong were the responses?

Both brepocitinib doses met the primary efficacy endpoint. Mean CSAMI-A scores fell 22.3 points with 45 mg and 22.2 points with 15 mg, compared with a 0.7-point reduction with placebo. Both comparisons reached P < .001.

Treatment-associated improvements appeared by week 4 and continued through week 16. The 45-mg group produced the strongest results across the trial’s stricter responder and remission-oriented measures.

• 69.2% achieved clear or almost-clear skin with at least a 2-category improvement on the Cutaneous Sarcoidosis Activity–Investigator Global Assessment, versus 0% receiving placebo.
• 76.9% achieved at least a 50% reduction in CSAMI-A, versus 0% receiving placebo.
• 100% achieved a CSAMI-A reduction of at least 10 points, versus 14.3% receiving placebo.
• 61.5% achieved a CSAMI-A score below 5, indicating minimal residual activity, versus 0% receiving placebo.

Did benefits extend to lupus pernio?

Among participants with lupus pernio receiving brepocitinib 45 mg, all achieved a CSAMI-A reduction of at least 10 points by week 16. The corresponding rate was 25% among placebo recipients.

That finding carries particular clinical weight because lupus pernio can cause irreversible tissue damage and disfigurement. Participants also improved despite the protocol-mandated discontinuation of systemic glucocorticoids, suggesting that disease control persisted without continued oral steroid therapy during the study period.

Did skin-related quality of life improve?

Patient-reported outcomes favored the 45-mg dose across three measures at week 16.

• Skindex-16 scores improved by a mean 23.5 points, versus an 8.9-point worsening with placebo; P = .003.
• Mean improvement on the King’s Sarcoidosis Questionnaire–Skin Domain reached 34.6 points with brepocitinib, versus 1.8 points with placebo; P = .005.
• Every participant receiving 45 mg reported improvement on the Patient Global Impression of Change, compared with 29% receiving placebo; P = .001.

Rosenbach said: “These published findings bring rigorous clinical evidence to a historically neglected disease and patient population.” The result supports further testing in cutaneous sarcoidosis, not approval for that indication.

What did the safety findings show?

Adverse events occurred in 92% of participants receiving 45 mg, 82% receiving 15 mg and 86% receiving placebo. Most events were mild. No deaths or serious adverse events were reported.

Investigators observed no malignancy, viral reactivation, major adverse cardiovascular events, venous thromboembolism or liver enzyme elevation. Two nonserious adverse events of special interest occurred in the 45-mg group: elevated creatine kinase and worsening of preexisting anemia.

The creatine kinase elevation improved during continued treatment, while the anemia resolved after treatment discontinuation. One participant in each treatment group permanently discontinued treatment because of an adverse event. Longer-term safety data will be needed to define brepocitinib’s benefit-risk profile in cutaneous sarcoidosis.

What happens next?

Priovant Therapeutics is advancing brepocitinib 45 mg once daily in the phase 3 BEACON+ trial. The company expects to enroll approximately 140 patients across 70 global sites, randomizing participants to brepocitinib 45 mg or placebo. The phase 2 study is registered as NCT06978725.

BEACON+ will measure the proportion of patients achieving at least a 50% reduction in CSAMI-A at week 16. Topline results are expected in 2028.

Brepocitinib already has FDA approval for adults with dermatomyositis under the brand name Lisraya. It remains investigational for cutaneous sarcoidosis. Investigators also cited the small phase 2 sample and the study’s inability to assess treatment effects on extracutaneous disease.

The 2028 topline readout will test whether the phase 2 signal holds in a larger, globally distributed placebo-controlled cohort.