TY - JOUR
T1 - Povorcitinib for hidradenitis suppurativa
T2 - the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials
AU - Porter, Martina L.
AU - Martorell, Antonio
AU - Sayed, Christopher J.
AU - Bechara, Falk G.
AU - Lev-Tov, Hadar
AU - Hsiao, Jennifer L.
AU - Frew, John W.
AU - Reguiaï, Ziad
AU - Gooderham, Melinda J.
AU - Goldfarb, Noah
AU - van der Zee, Hessel H.
AU - del Marmol, Veronique
AU - Marzano, Angelo V.
AU - Ehst, Benjamin D.
AU - Ackerman, Lindsay S.
AU - Hayama, Koremasa
AU - Tian, Chenwei
AU - Kelley, Jennifer
AU - Zhen, Huiling
AU - Kirby, Joslyn S.
AU - Brown, Kurt
AU - Santos, Leandro L.
AU - Zouboulis, Christos C.
N1 - Publisher Copyright:
© Incyte Corporation and the Authors 2026.
PY - 2026/8
Y1 - 2026/8
N2 - Although therapeutic options for hidradenitis suppurativa (HS) continue to expand, unmet needs remain substantial. We evaluated the efficacy and safety of povorcitinib (an oral, highly selective Janus kinase 1 (JAK1) inhibitor) in patients with moderate to severe HS in two randomized trials. STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled phase 3 trials. Adults with moderate to severe HS were randomized 2:2:1:1 to once-daily treatment through week 54: povorcitinib 45 mg; povorcitinib 75 mg; placebo with crossover at week 12 to povorcitinib 45 mg; or placebo with crossover at week 12 to povorcitinib 75 mg. The primary endpoint was HiSCR50 (≥50% decrease in total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count) at week 12. STOP-HS1/STOP-HS2 enrolled 608/619 patients, respectively. In both studies, both povorcitinib doses met the primary endpoint; in STOP-HS1, 82/204 (40%) patients in the povorcitinib 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in the placebo group achieved HiSCR50 (OR (95% CI) 45 mg: 1.6 (1.1−2.5), P = 0.0240; 75 mg: 1.6 (1.1−2.4), P = 0.0214); corresponding values for STOP-HS2 were 88/208 (42%) and 88/208 (42%) versus 58/203 (29%; OR (95% CI) 45 mg: 1.8 (1.2−2.8), P = 0.0035; 75 mg: 1.9 (1.2−2.8); P = 0.0033). Through week 12, across STOP-HS1/STOP-HS2, serious treatment-emergent adverse events (AEs) occurred in 1−2% of patients across povorcitinib doses and in 2−3% with placebo; through week 54, serious AEs occurred in 5%/6% of patients receiving 45-mg/75-mg povorcitinib, respectively. The most frequent AEs among patients treated with 45-mg/75-mg povorcitinib were acne (17%/20%), nasopharyngitis (10%/12%) and upper respiratory tract infection (11%/10%). One death of undetermined etiology was reported and deemed unrelated to treatment. No new or unexpected safety findings were identified. Oral povorcitinib demonstrated significant improvements in HiSCR50 versus placebo and a favorable safety profile in patients with moderate to severe HS. ClinicalTrials.gov registration: NCT05620823 and NCT05620836.
AB - Although therapeutic options for hidradenitis suppurativa (HS) continue to expand, unmet needs remain substantial. We evaluated the efficacy and safety of povorcitinib (an oral, highly selective Janus kinase 1 (JAK1) inhibitor) in patients with moderate to severe HS in two randomized trials. STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled phase 3 trials. Adults with moderate to severe HS were randomized 2:2:1:1 to once-daily treatment through week 54: povorcitinib 45 mg; povorcitinib 75 mg; placebo with crossover at week 12 to povorcitinib 45 mg; or placebo with crossover at week 12 to povorcitinib 75 mg. The primary endpoint was HiSCR50 (≥50% decrease in total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count) at week 12. STOP-HS1/STOP-HS2 enrolled 608/619 patients, respectively. In both studies, both povorcitinib doses met the primary endpoint; in STOP-HS1, 82/204 (40%) patients in the povorcitinib 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in the placebo group achieved HiSCR50 (OR (95% CI) 45 mg: 1.6 (1.1−2.5), P = 0.0240; 75 mg: 1.6 (1.1−2.4), P = 0.0214); corresponding values for STOP-HS2 were 88/208 (42%) and 88/208 (42%) versus 58/203 (29%; OR (95% CI) 45 mg: 1.8 (1.2−2.8), P = 0.0035; 75 mg: 1.9 (1.2−2.8); P = 0.0033). Through week 12, across STOP-HS1/STOP-HS2, serious treatment-emergent adverse events (AEs) occurred in 1−2% of patients across povorcitinib doses and in 2−3% with placebo; through week 54, serious AEs occurred in 5%/6% of patients receiving 45-mg/75-mg povorcitinib, respectively. The most frequent AEs among patients treated with 45-mg/75-mg povorcitinib were acne (17%/20%), nasopharyngitis (10%/12%) and upper respiratory tract infection (11%/10%). One death of undetermined etiology was reported and deemed unrelated to treatment. No new or unexpected safety findings were identified. Oral povorcitinib demonstrated significant improvements in HiSCR50 versus placebo and a favorable safety profile in patients with moderate to severe HS. ClinicalTrials.gov registration: NCT05620823 and NCT05620836.
UR - https://www.scopus.com/pages/publications/105045401353
UR - https://www.scopus.com/pages/publications/105045401353#tab=citedBy
U2 - 10.1038/s41591-026-04534-z
DO - 10.1038/s41591-026-04534-z
M3 - Article
C2 - 42493571
AN - SCOPUS:105045401353
SN - 1078-8956
VL - 32
SP - 3071
EP - 3081
JO - Nature Medicine
JF - Nature Medicine
IS - 8
ER -