Treatment with povorcitinib, an oral JAK1 inhibitor, resulted in significant improvements among patients with moderate-to-severe hidradenitis suppurativa (HS) in two phase 3 trials, providing evidence that the drug may present an alternative to injectable biologics.

STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled, multinational trials that included 1227 adults with moderate-to-severe HS randomly assigned to once-daily povorcitinib 45 mg, povorcitinib 75 mg, or placebo. The results were published in Nature Medicine on July 23.

Current FDA-approved treatments for moderate-to-severe HS are adalimumab (a TNF inhibitor), secukinumab (an interleukin [IL]-17A inhibitor), and bimekizumab (an IL-17A/IL-17F inhibitor), all of which are administered subcutaneously.

“Povorcitinib offers a different mechanism of action from direct cytokine inhibition to reduce inflammatory lesion burden in HS, reduce skin pain, and reduce flare frequency,” Amit Garg, MD, professor and chair of the Department of Dermatology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Uniondale, New York, told Medscape Medical News. When available, “povorcitinib may be used first-line in the appropriate patient and will also be used in HS patients who have an inadequate response to TNF or IL-17 inhibitors.”

Based on STOP-HS data, the manufacturer, Incyte, has submitted a New Drug Application with the FDA and a Marketing Authorization Application with the European Medicines Agency for povorcitinib as a treatment for HS, which are now under review, according to the company.

“I think povorcitinib is going to be a wonderful addition to the FDA-approved therapies that we currently have for hidradenitis suppurativa,” Barry Resnik, MD, voluntary clinical professor in the Department of Dermatology and Cutaneous Surgery at the University of Miami, Miami, told Medscape Medical News. “It was effective for a wide variety of patients with little to no side effects,” said Resnik, who practices in Miami.

The studies enrolled adults who had previously had an inadequate response, intolerance, or contraindication to systemic therapy at 103 sites (STOP-HS1) and 99 sites (STOP-HS2) across Australia, Canada, Europe, Japan, and the US. Participants were randomly assigned to povorcitinib 45 mg, povorcitinib 75 mg, or placebo once a day. After the initial 12-week placebo-controlled period, placebo recipients crossed over to active treatment. All patients were followed through 54 weeks.

The studies’ primary endpoint was Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) at week 12, defined as at least a 50% reduction in abscess and inflammatory nodule count without worsening of abscesses or draining tunnels.

At week 12, in STOP-HS1, HiSCR50 was achieved by 40% and 41% of patients receiving the 45-mg and 75-mg doses (45 mg, P = .0240; 75 mg, P = .0214) compared with 30% of patients receiving placebo.

Similar findings were observed in STOP-HS2, where 42% of patients in both active-treatment groups achieved HiSCR50 compared with 29% of those in the placebo group (45 mg, P = .0035; 75 mg, P = .0033).

Notably, clinical improvement emerged rapidly and remained durable, with responses detectable as early as week 3 and efficacy maintained through 54 weeks, the authors reported. Continued reductions in lesion counts were observed during the extension period.

“With a JAK inhibitor, we have a wider spectrum of effectiveness,” study coauthor Christos Zouboulis, MD, PhD, professor of dermatology and venereology at the Brandenburg Medical University and head of the Department of Dermatology, Venereology, and Immunology at Universitätsklinikum Ruppin-Brandenburg in Neuruppin, Germany, told Medscape Medical News. “We not only attack one single molecule; we attack a pathway.”

While HiSCR50 was the primary outcome, investigators evaluated another measure — the International Hidradenitis Suppurativa Severity Score System (IHS4), which assesses the severity of HS by counting and weighting skin lesions, inflammatory nodules, abscesses, and draining tunnels — to evaluate efficacy.

“The HiSCR50 is a primary outcome and something that the FDA wants, but in reality, it does not give the real response rate,” Zouboulis said. “That’s why we also leaned on the secondary outcome, which is the IHS4…. After 16 weeks and then 54 weeks, we went up to 60% improvement of the IHS4, which is as good as the injectables, in some cases a little bit more, some cases a little bit less, but it is comparable. So we can say we have an oral drug, and this drug is as effective as the approved injected drugs, plus or minus.”

Safety findings were generally consistent with previous findings for JAK inhibitors. Serious treatment-emergent adverse events were uncommon and similar to those in placebo groups. Over 54 weeks, the most frequently reported adverse events were acne, nasopharyngitis, and upper respiratory tract infections among those treated with povorcitinib.

This study was sponsored by Incyte. Garg and Resnik served as consultants to Incyte but were not involved with the current study.

Zouboulis’ disclosures include receiving consultancy/advisory board disease-relevant honoraria from Almirall, Boehringer Ingelheim, Eli Lilly, Idorsia, Incyte, MSD, Novartis, Pfizer, Sanofi, Takeda, UCB, and Zura Bio; speaker fees from Bristol Myers Squibb, Novartis, and UCB. Garg also disclosed being a medical consultant to other companies with drug development programs for HS. Resnik also reported serving as a consultant to Novartis, as well as a consultant and principal investigator for MoonLake Immunotherapeutics.

Scott Harris has covered dermatology, rheumatology, and assorted healthcare topics for various news outlets and nonprofit organizations for more than a decade. He lives near Washington, DC.