Povorcitinib Improves Moderate to Severe Hidradenitis Suppurativa at Week 24

Treatment of moderate to severe hidradenitis suppurativa (HS) with povorcitinib therapy will lead to clinically meaningful and statistically significant HS improvements through Week 24, according to new late-breaking data.1,2

These 24-week interim findings resulted from the pivotal phase 3 STOP-HS program evaluating povorcitinib (INCB54707), a highly selective oral JAK1 inhibitor, in adults ≥18 years. The data were presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France.

“HS is a complex and often misunderstood condition that can profoundly affect patients’ daily lives,” Martina J. Porter, MD, STOP-HS study investigator, assistant professor of dermatology at Harvard Medical School, and vice chair for research and academics at Beth Israel Deaconess Medical Center, said in a statement.1 “Data from the STOP-HS clinical trial program highlight the potential of povorcitinib to address key signs and symptoms for those living with HS, and it is encouraging to see advancements in potential new, effective treatment options for this patient community.”

HS itself is a chronic, progressive inflammatory skin condition marked by painful nodules and abscesses that can lead to permanent scarring and tissue damage. Disregulation of the JAK/STAT pathway is thought to impact the inflammatory processes underlying this disease. 150,000 people are estimated to live in the US with moderate to severe forms of HS, which can have significant effects on quality of life.

Povorcitinib is an oral small-molecule JAK1 selective inhibitor which the investigators highlighted is currently in phase 3 clinical trials for vitiligo, HS, and prurigo nodularis, as well as phase 2 2 studies highlighting asthma and chronic spontaneous urticaria (CSU). To evaluate this drug, the STOP-HS program was conducted. It includes two phase 3 studies, STOP-HS1 (NCT05620823) and STOP-HS2 (NCT05620836), with each enrolling approximately 600 subjects.

Eligible participants had a diagnosis of moderate to severe HS for at least 3 months prior to screening, were ≥18 years of age, showed a total abscess and inflammatory nodule (AN) count of ≥5, reported lesions in at least 2 anatomical regions, and had a documented history of inadequate response, intolerance, or contraindication to at least 3 months of conventional systemic medications.

Both of these trials involved a 12-week double-blind, placebo-controlled treatment period, followed by a 42-week extension and a 30-day safety follow-up. Povorcitinib at both 45 mg and 75 mg once-per-day met the primary endpoint in each of the studies.1 A significantly greater proportion of patients achieved Hidradenitis Suppurativa Clinical Response (HiSCR50; ≥50% reduction in total AN count from baseline without worsening in abscesses or draining tunnels) compared to patients with placebo at the 12-week mark:

STOP-HS1:

• 45 mg: 40.2% versus 29.7% (P= .024)
• 75 mg: 40.6% versus 29.7% (P= .0214)

STOP-HS2:

• 45 mg: 42.3% versus 28.6% (P= .0035)
• 75 mg: 42.3% versus 28.6% (P= .0033)

At Week 12, patients receiving povorcitinib were also more likely than placebo recipients to achieve HiSCR75 (≥75% AN reduction), at least a 3-point reduction in the Skin Pain Numeric Rating Scale (NRS), Skin Pain NRS30 (≥30% pain reduction), and had fewer HS flares.

In their exploration of extended efficacy outcomes, the investigative team found that, by Week 24, approximately 60% of trial subjects given povorcitinib (both doses) attained HiSCR50. The proportions across the trials were:

STOP-HS1:

• 45 mg: 52.9%–64.0%
• 75 mg: 50.0%–62.7%

STOP-HS2:

• 45 mg: 57.1%–58.0%
• 75 mg: 56.3%–58.5%

Higher thresholds of response were also observed at the 24-week mark across both of the studies:

• HiSCR75: 31.0%–40.3%
• HiSCR90: 13.8%–27.7%
• HiSCR100: 9.2%–21.3%

Improvements in patients' level of skin pain were sustained, with reductions being observed as early as Week 3 and continuing through Week 24. At this timepoint, 62%–70% of patients on povorcitinib reported mild or no pain.

In patients with at least a single draining tunnel at baseline, achievement of complete resolution of tunnels (dt100) took place in:

• Week 12: 34.6% (45 mg) and 41.6% (75 mg)
• Week 24: 39.0% (45 mg) and 50.6% (75 mg)

Consistency was observed by Porter and colleagues in the safety profile of povorcitinib with earlier reports. Occurrences of treatment-emergent adverse events (TEAEs) appeared in 42.4%–54.3% of individuals involved who switched from placebo to povorcitinib at the 12. Among 70.2%–78.7% of those initially randomized to active treatment by the 24-week mark. Porter et al found serious adverse events took place in 2.9%–4.8% of subjects.

They noted, however, that adverse events of special interest (AESIs) were seen among 0%–1.4% of participants. They also found a lack of major adverse cardiovascular events (MACE) or deaths took place in their study period. These data are expected to support regulatory submissions in Europe in 2025 and in the US around early 2026.

References

1. Porter M, Martorell A, Santos L, et al. Povorcitinib for Moderate to Severe Hidradenitis Suppurativa: Week 24 Interim Phase 3 Results. Presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress, Sept 17-20, 2025.

2. Incyte Announces New 24-Week Phase 3 Data from the STOP-HS Clinical Trial Program of Povorcitinib in Hidradenitis Suppurativa at EADV 2025. Incyte. September 17, 2025. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-new-24-week-phase-3-data-stop-hs-clinical-trial.