DENVER — An experimental oral JAK1 inhibitor showed durable benefit in patients with moderate-to-severe hidradenitis suppurativa (HS) through more than a year of treatment, a pair of identical placebo-controlled phase 3 trials found.

At 54 weeks in the STOP-HS1 and STOP-HS2 trials, up to 71.4% of patients taking povorcitinib achieved at least a 50% reduction from baseline in the total abscess and inflammatory nodule (AN) count, reported Martina L. Porter, MD, assistant professor and vice chair for research and academics in the Department of Dermatology at Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, in a presentation at American Academy of Dermatology (AAD) 2026 annual meeting.

On another measure, up to 29% of patients treated with povorcitinib reached a 100% decrease in AN count with no increase in abscesses or draining tunnels by 54 weeks.

“HS is not a disease that is treatable in 12-16 weeks,” Porter said. “In the clinical arena, we are really interested in what happens to patients over a year’s time.”

A Need for Better Therapies

Three injectable biologics are approved for HS — adalimumab, secukinumab, and bimekizumab. “While these achieve great results in some patients, at least half will have inadequate responses and need to consider other options,” said Christopher Sayed, MD, professor of dermatology, The University of North Carolina at Chapel Hill, who’s familiar with the study findings but didn’t take part in the research.

According to the AAD presentation, povorcitinib is an oral, highly selective JAK1 inhibitor that’s being studied as a treatment for inflammatory conditions such as HS.

Study Methodology and Demographics

The STOP-HS1 (N = 608) and STOP-HS2 (N = 619) trials enrolled patients in North America, Europe, Japan, and Australia with moderate-to-severe HS, an AN count ≥ 5 in ≥ 2 anatomic areas, Hurley stage II or III, HS diagnosis for ≥ 3 months, and prior treatment with a systemic therapy (oral antibiotic or biologic).

Among participants overall, the median age was 37 years, 62.8% were women, 74.6% were White and 14.2% were Black individuals, mean BMI was 34.0, and nearly half were current smokers. Mean disease duration was 10.3 years, 37.2% had prior biologic exposure, and mean AN count was 12.0.

Patients were randomized 1:1:1 to povorcitinib 45 mg once daily, povorcitinib 75 mg once daily, or placebo. At 12 weeks, the placebo group switched to one of the two povorcitinib doses, and all participants then continued in an open-label extension for 42 weeks.

Study Results: Lasting Improvement

The primary endpoint was at least a 50% reduction from baseline in the abscess and inflammatory nodule count with no increase in abscesses or draining tunnels (HiSCR50) at week 12.

In STOP-HS1, 40.6% (75 mg) and 40.2% (45 mg) of those in the povorcitinib groyp reached this mark vs 29.7% in the placebo group (P < .025). In STOP-HS2, 42.3% of those on each doses reached that mark vs 28.6% of those on placebo at week 12 (P < .010).

At 54 weeks, the percentages reaching this endpoint among the various cohorts — some started by taking povorcitinib while others switched to it from placebo — ranged from 60.2% to 68.3% in STOP-HS1 and 57.3% to 71.4% in STOP-HS2.

Also at 54 weeks, the proportion of treated patients reaching a 100% decrease in AN count with no increase in abscesses or draining tunnels (HiSCR100) were 19.0%-29.0% in STOP-HS1 and 17.9%-27.2% in STOP-HS2.

Several measures of quality of life also improved by week 54.

Adverse Effects Roundup

Up to week 54, among the various cohorts taking povorcitinib, including those who crossed over from placebo, rates of any treatment-emergent adverse effects (TEAEs) ranged from 76.2% to 83.4%, and rates of treatment-related adverse effects ranged from 36.9% to 48.2%. (Adverse effect data for the placebo groups was not provided.)

The most common TEAEs were acne, nasopharyngitis, and upper-respiratory tract infection.

There was one major adverse cardiovascular event (MACE) in a patient on the 45 mg dose, and three cases of deep vein thrombosis (DVT)/pulmonary embolism in patients on either dose.

As Porter noted, “when we think of JAK inhibitors, we often think about some of the side-effect profiles and the black-box warning that exists on the currently approved JAK inhibitors for DVT and MACE events.”

Dropouts Were Common

The number of participants in STOP-HS1 fell from 608 at baseline to 368 at 54 weeks, and the number in STOP-HS2 fell from 619 to 350.

“It’s become harder and harder to maintain patients in HS clinical trials,” Porter said in response to a question about the drop-out rate. “I think this is due to the fact that there’s probably 20 other ongoing trials in development now, as well as many more medications available through clinical practice.”

Also, “we’re not seeing efficacy rates like we see for psoriasis, where people are hitting PASI [Psoriasis Area and Severity Index] 100. I think they’re actually looking for other options.”

Outside Perspective: Big ‘New Role’ for Povorcitinib

The “biggest new role” for povorcitinib is that it’s set to be “the first oral small molecule approved for HS,” Sayed told Medscape Medical News. “This will be a huge advantage for patients wary of home injections, and it will provide a new mechanism of action for those who have failed or have contraindications to other treatments.”

Sayed said that he’s seen that “patients who have a lot of inflammatory nodules are highly responsive to JAK inhibitors, as are those on the opposite end of the disease spectrum that are very severe and have almost cutaneous Crohn’s-like presentations.”

The adverse effect profile is reassuring, he added. “While earlier safety concerns around tofacitinib [used to treat conditions such as rheumatoid arthritis] created some fear around JAK inhibitors, data has been overwhelmingly reassuring for JAK1 inhibitors.”

As for expense, “cost will likely be high and insurance authorizations will be required, but there will likely be good support to make it affordable for most patients who need it,” he said.

Incyte funded the studies. Porter disclosed having relationships with more than 20 drugmakers, including Incyte. Sayed disclosed having relationships with Incyte, UCB, AbbVie, and Novartis.