The Emerging Role of Povorcitinib in Moderate to Severe Hidradenitis Suppurativa

One of the perks of being a hidradenitis suppurativa (HS) doctor is hearing these sentences: ‘Doctor, you saved my life,’” Hadar Lev-Tov, MD, MAS, said in a recent Dermatology Times Between the Lines video series.

HS management is entering a new therapeutic era, as highlighted in this journal club series with Lev-Tov and Martina Porter, MD. The clinicians focused on the phase 3 STOP-HS 1 (NCT05620823) and 2 (NCT05620836) trials of povorcitinib, an oral Janus kinase 1 (JAK1)–selective inhibitor for moderate to severe HS. Lev-Tov is an associate professor of clinical dermatology and cutaneous surgery at the University of Miami in Florida, and Porter is a dermatologist and vice chair of research and academics at Beth Israel Deaconess Medical Center in Boston, Massachusetts. She is also an assistant professor of dermatology at Harvard Medical School.

Addressing the Efficacy Gap in Current Care

Despite advances over the past decade, both clinicians emphasized that HS treatment outcomes remain inadequate compared with other inflammatory skin diseases. Patients often experience a slow onset of response to therapy, particularly in severe disease, and even with current best treatments, many achieve only partial improvement.

“We don’t have great treatment still for this disease,” Porter said. “When we really look at the efficacy, we’re still kind of lingering in this 50% to 75% improvement in disease state, and for maybe just over half of patients.”

In addition, optimal care frequently requires a complicated combination of medical, procedural, and surgical approaches. In practice, dermatology clinicians often escalate treatment earlier than trial definitions suggest, especially in patients with early tunnel formation, strong family history, or significant quality-of-life impairment.

Current FDA-approved systemic therapies for HS include biologics such as adalimumab, secukinumab, and bimekizumab. However, both Lev-Tov and Porter noted that biologics are underused in HS despite their benefits.

“The data is pretty clear that we are, as dermatologists, underutilizing these great medications,” Lev-Tov said. “And for those of you who are still timid out there thinking about using biologics for your patients with HS.... It’s time to do this.”

A Novel Oral Mechanism

Povorcitinib, as a JAK1-selective oral agent, differs from cytokine-specific biologics and may be particularly useful in patients with comorbid inflammatory conditions or those who have not responded adequately to biologics. Importantly, JAK inhibitors may ultimately be used across a wider range of disease severities rather than reserved only for the most refractory cases.

The STOP-HS 1 and 2 trials were large, global phase 3 studies with a 12-week placebo-controlled period, followed by a 24-week extension. Adult patients with moderate to severe HS were included, defined by abscess and nodule counts, involvement of multiple anatomic areas, and Hurley stage II or III disease. Baseline characteristics reflected a relatively severe and diverse HS population, with long disease duration, substantial lesion burden, and over one-third of patients having previously received biologics.

At week 12, Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) rates were as follows:

STOP-HS 1 placebo: just under 30%

• Povorcitinib 45 mg: approximately 40%
• Povorcitinib 75 mg: approximately 40%
• STOP-HS 2 placebo: approximately 28.6%
• Povorcitinib 45 mg: approximately 42%
• Povorcitinib 75 mg: approximately 42%

Responses improved over time, with week 24 HiSCR50 rates approaching 50% to 58% among continuously treated patients and exceeding 60% in those who crossed over from placebo.

Higher response thresholds, including HiSCR75 and HiSCR90/100, were achieved more frequently with povorcitinib, particularly at the higher dose. Although complete clearance remains uncommon, even small percentages of patients reaching these end points represent meaningful clinical benefit in HS.

Tolerability and Pain Reduction

Pain reduction emerged as a particularly important outcome, which Porter noted could be the most debilitating part of this disease. At baseline, most patients reported moderate to severe pain, but by week 12, a substantial number reported no or mild pain, with further improvement by week 24. Improvements in draining tunnels were also notable. A significant proportion of patients achieved complete resolution of draining tunnels by weeks 12 and 24, especially at the higher dose.

In terms of safety, povorcitinib was generally well tolerated. The investigators observed no major adverse cardiovascular events or venous thromboembolic events during the initial 12-week period. Common adverse events included acne, headache, and nasopharyngitis, with acne showing a dose-dependent pattern but remaining manageable. Laboratory abnormalities were limited and consistent with JAK1 selectivity.

“When it comes to JAK inhibitors and dermatology, we have to keep in mind: What is the trade‑off here? What is the trade‑off in the severity of the disease and the risk that the patients are willing to take? And I would argue that in HS, it’s not insignificant,” Lev-Tov said.

Clinical Outlook

From a practical perspective, clinicians are advised to allow at least 12 weeks to assess efficacy, recognizing that responses often deepen over several months. Early signs of improvement are important; lack of response by 8 to 12 weeks may warrant dose adjustment or a change in therapeutic mechanism. Treatment sequencing will remain individualized, with many patients requiring trials of multiple agents due to the heterogeneity of HS.

If approved, povorcitinib would represent the first oral systemic therapy specifically indicated for HS, offering an alternative to injectable biologics. Its once-daily dosing and broad immunologic activity may make it an important addition to the therapeutic armamentarium, particularly for patients with significant pain, drainage, and tunnel formation.

“We’re familiar with JAK inhibitors in general, but we don’t have povorcitinib approved for any disease states right now,” Porter said. “It will be extremely nice to have a totally different mechanism of action for these patients.”