Povorcitinib Improves Clinical Response in Moderate-to-Severe Hidradenitis Suppurativa

Once-daily oral povorcitinib significantly improved clinical response compared with placebo in patients with moderate-to-severe hidradenitis suppurativa (HS), with consistent findings across 2 phase 3 trials.

Investigators evaluated the efficacy and safety of povorcitinib, a highly selective Janus kinase 1 (JAK1) inhibitor, in the identically designed STOP-HS1 and STOP-HS2 randomized, double-blind, placebo-controlled trials. The studies enrolled 608 and 619 adults with moderate-to-severe HS, respectively.

Participants were randomized 2:2:1:1 to receive povorcitinib 45 mg, povorcitinib 75 mg, placebo followed by crossover to povorcitinib 45 mg at week 12, or placebo followed by crossover to povorcitinib 75 mg at week 12. Once-daily treatment continued through week 54.

The primary endpoint was achievement of Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) at week 12, defined as at least a 50% reduction from baseline in total abscess and inflammatory nodule count without an increase in abscess or draining tunnel count.

Both povorcitinib doses met the primary endpoint in both trials.

In STOP-HS1, HiSCR50 was achieved by 82 of 204 patients (40%) receiving povorcitinib 45 mg and 82 of 202 (41%) receiving 75 mg compared with 60 of 202 (30%) receiving placebo. The odds ratios (ORs) vs placebo were 1.6 for both the 45-mg dose (95% CI, 1.1-2.5; P=.0240) and 75-mg dose (95% CI, 1.1-2.4; P=.0214).

Results were similar in STOP-HS2. HiSCR50 was achieved by 88 of 208 patients (42%) in each povorcitinib group compared with 58 of 203 (29%) receiving placebo. The ORs were 1.8 with povorcitinib 45 mg (95% CI, 1.2-2.8; P=.0035) and 1.9 with 75 mg (95% CI, 1.2-2.8; P=.0033).

Through week 12, serious treatment-emergent adverse events occurred in 1% to 2% of patients across povorcitinib doses compared with 2% to 3% receiving placebo. Through week 54, serious adverse events occurred in 5% of patients receiving povorcitinib 45 mg and 6% receiving 75 mg.

The most frequently reported adverse events with the 45-mg and 75-mg doses, respectively, were acne (17% and 20%), nasopharyngitis (10% and 12%), and upper respiratory tract infection (11% and 10%). One death of undetermined etiology occurred and was considered unrelated to treatment.

“No new or unexpected safety findings were identified,” the investigators reported.

The authors concluded that oral povorcitinib “demonstrated significant improvements in HiSCR50 vs placebo and a favorable safety profile” among patients with moderate-to-severe HS.

Reference
Porter ML, Martorell A, Sayed CJ, et al. Povorcitinib for hidradenitis suppurativa: the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials. Nat Med. 2026;32(8):3071-3081. doi:10.1038/s41591-026-04534-z