Phase 3 Trials of Oral Povorcitinib Show Positive Results in Hidradenitis Suppurativa

Incyte has announced positive topline data of two phase 3 trials of povorcitinib in adult patients with moderate to severe hidradenitis suppurativa (HS).

Hidradenitis suppurativa is an autoimmune condition that attacks hair follicles. It is characterized by painful nodules, abscesses and pus-filled channels typically found in the armpits, groin and buttocks. Severe flareups often leave scars. It currently affects about 1% of the United States population and is more common in women, with an onset around puberty, according to the HS Foundation.

“Hidradenitis suppurativa is a challenging and debilitating condition without a cure. Given the limitations of current HS treatments and their impact on patients’ daily lives, there is a critical need for new, well-tolerated, and effective therapies that provide a rapid reduction in the signs and symptoms of HS, in particular pain,” Steven Stein, M.D., chief medical officer at Incyte, said in a news release.

HS is complex, involving multiple cell types and cytokines and several linked to JAK1 signaling.

Joslyn Kirby, M.D.

“Much has been learned recently about the pathogenesis of HS. In contrast to other dermatoses where a single axis of the immune system is dominant, hidradenitis is complex and heterogenous, with multiple cell types and cytokines implicated. This may explain the limited efficacy of some therapies since the approved therapies are injectable monoclonal antibodies specific to certain interleukins,” Joslyn Kirby, M.D., senior medical director, inflammation and autoimmunity at Incyte, said during a call with investors last week.

Several therapies are approved to treat HS, including Humira (adalimumab) and some of its biosimilars, Cosentyx (secukinumab), and Bimzelx (bimekizumab), which was approved in November 2024.

Povorcitinib is an oral small-molecule JAK1 inhibitor. Kirby explained that JAK1 inhibition is involved across multiple cytokines and disease states. “As a small molecule, povorcitinib is also differentiated because of its oral administration. As a highly selective JAK1 inhibitor, povorcitinib can modulate multiple cytokines in HS pathogenesis.”

The STOP-HS clinical trial program includes two phase 3 studies, STOP-HS1 and STOP-HS2, that evaluated the efficacy and safety of povorcitinib in about 600 adult patients with moderate to severe HS. Both studies include a 12-week placebo-controlled treatment period, followed by a 42-week extension period and 30-day safety follow-up.

The primary endpoint for both studies is the proportion of patients who achieved hidradenitis Suppurativa Clinical Response (HiSCR), a ≥50% reduction from baseline in the total abscess and inflammatory nodule count. Key secondary endpoints include the proportion of patients achieving a 75% reduction in inflammatory nodule count with no increase from baseline in abscess or draining tunnel count.

In the trials, after 12 weeks, 40.2% to 42.3% of patients who received the lower dose had a 50% decrease in boils and abscesses. In the high-dose group, 40.6% to 42.3% of patients met the same mark.

The most frequent treatment-emergent adverse events were acne, headache, nasopharyngitis and upper respiratory tract infection.

Company officials anticipate filing a new drug application (NDA) for povorcitinib in late 2025 to early 2026.

Povorcitinib is also being studied in phase 3 clinical trials to treat patients with vitiligo and prurigo nodularis (PN), as well as phase 2 trials to treat patients with asthma and chronic spontaneous urticaria (CSU).