Povorcitinib Shows Sustained 54-Week Efficacy in HS, Benefits Patients Previously on Anti-TNF Therapy

This content was developed independently and is not endorsed by the American Academy of Dermatology.

Povorcitinib (Incyte), an oral Janus kinase 1 (JAK1) inhibitor, demonstrated durable efficacy and a favorable safety profile through 54 weeks in patients with moderate to severe hidradenitis suppurativa (HS), including those previously treated with anti–tumor necrosis factor (TNF) therapy, according to 2 posters from the 2026 American Academy of Dermatology (AAD) Annual Meeting.^1,2

HS, a chronic, recurrent inflammatory condition, is characterized by painful skin nodules and abscesses that can progress to tunnels, irreversible tissue damage, and scarring. Its pathophysiology is complex and involves multiple cell types and cytokines, several of which signal through JAK1.

Adalimumab (Humira; AbbVie), an anti–TNF-α monoclonal antibody, became the first therapy approved for moderate to severe HS in 2015. However, in pivotal studies, many patients treated with adalimumab did not achieve Hidradenitis Suppurativa Clinical Response (HiSCR50) by week 12, defined as at least a 50% reduction in abscess and inflammatory nodule count with no increase in abscesses or draining tunnels.

By contrast, povorcitinib met the primary end point of HiSCR50 with both 45- and 75-mg doses at week 12 in the phase 3 STOP-HS1 (NCT05620823) and STOP-HS2 (NCT05620836) studies. The study populations included patients with moderate to severe HS who had an inadequate response to at least 1 conventional systemic therapy, including oral antibiotics or biologics, with approximately 37% being biologic-experienced.

Two posters presented at the 2026 AAD Annual Meeting built on these findings: one featured in a late-breaking session earlier today presented 54-week long-term results, while the other detailed a 24-week interim analysis in an anti–TNF–experienced patient subgroup.

Late-Breaking Data Show Durable 54-Week Efficacy of Povorcitinib in HS

Presented by lead author Martina L. Porter, MD, Harvard Medical School, the first poster evaluated the efficacy and safety of povorcitinib through week 54 in patients with moderate to severe HS enrolled in STOP-HS1 and STOP-HS2.¹

The phase 3 trials were identically designed, randomized, double-blind, and placebo-controlled. Patients were randomized 1:1:1 to once-daily povorcitinib 45 mg, 75 mg, or placebo for 12 weeks, followed by a 42-week extension period. During the extension, participants who received 45 mg or 75 mg of povorcitinib continued their same dose, while those initially assigned to placebo were rerandomized to receive 45 or 75 mg of povorcitinib.

The late-breaking data show that clinically meaningful and durable responses were observed through week 54 across both studies, with up to 71.4% of patients achieving HiSCR50. Porter highlighted that the trials also demonstrated higher-threshold responses, with up to 57% achieving HiSCR75 and up to 29% achieving HiSCR100.

Across both trials, povorcitinib treatment led to consistent reductions in all 3 key inflammatory lesion types: abscesses, inflammatory nodules, and draining tunnels. She noted that full clearance of inflammatory lesions was achieved in 16.1% to 20.2% of patients at week 54. Additionally, reductions were observed across draining tunnels (75 mg, up to −62.0%; 45 mg, up to −57.7%), inflammatory nodules (75 mg, up to −63.2%; 45 mg, up to −57.0%), and abscesses (75 mg, up to −63.7%; 45 mg, up to −62.9%).

Porter also said a high proportion of participants achieved clinically meaningful improvements in symptoms, including skin pain (40.5%-46.8%) and fatigue (49.0%-58.0%), as well as skin condition–related (59.4%-64.7%) and HS-specific (33.7%-40.2%) quality of life.

Regarding safety, both povorcitinib doses were well tolerated and remained consistent through 54 weeks, aligning with previously reported 24-week data. She noted that treatment-emergent adverse events (TEAEs) occurred in 76.2% to 83.4% of patients and were generally mild to moderate, with the most common being acne, nasopharyngitis, and upper respiratory tract infections. Porter added that grade 3 or higher TEAEs occurred in 5.4% to 8.0% of patients, resulting in low discontinuation rates (6.1%-9.4%).

Similarly, rates of adverse events of special interest, including herpes zoster, serious infections, opportunistic infections, malignancies, and thromboembolic events, were 2.3% or less across both studies.

These findings supported the submission of a new drug application for povorcitinib in HS, which is currently under review by the FDA.³

“Both doses of povorcitinib were generally well tolerated through 54 weeks of treatment, and this really does support the potential of oral povorcitinib for treatment of moderate to severe HS in the future,” Porter concluded.¹

24-Week Analysis Highlights Povorcitinib Benefit in Anti-TNF–Experienced Patients

A second poster narrowed the focus to patients who were anti-TNF–experienced, defined as those with an inadequate response, intolerance, or contraindication to anti-TNF biologic therapy.²

This 24-week analysis assessed the proportion of patients within the STOP-HS1 and STOP-HS2 trials achieving HiSCR50, HiSCR75, or HiSCR90, as well as at least a 3-point decrease on the Skin Pain Numerical Rating Scale (NRS). Safety outcomes included TEAEs and laboratory abnormalities.

Of the 1227 patients randomized across both trials, 457 (37.2%) had previously received at least 1 biologic therapy. Among these, 364 received anti-TNF treatment (29.7%), with 329 (90.4%) meeting criteria for inclusion in the anti–TNF-experienced subgroup.

Compared with the overall population, these patients had more severe disease severity at baseline, including longer mean disease duration (12.3 vs 10.3 years), higher Skin Pain NRS (6.0 vs 5.0), and greater draining tunnel (3.7 vs 2.8) and abscess and inflammatory nodule (14.3 vs 12.0) counts.

At week 12, both doses of povorcitinib demonstrated higher response rates vs placebo for HiSCR50, with continued improvement observed through week 24. Higher-threshold responses (HiSCR75 and HiSCR90) also improved over time.

Additionally, more patients receiving povorcitinib achieved at least a 3-point reduction in Skin Pain NRS as early as week 3, with the 45-mg dose reaching statistical significance at week 12. Regarding safety, povorcitinib demonstrated a favorable and consistent safety profile, with infrequent grade 3 or higher laboratory abnormalities during the 24-week treatment period.

"Even for patients who have not responded to TNF inhibitors such as adalimumab, which has been FDA approved for HS for more than a decade, povorcitinib can lead to excellent responses,” lead author Christopher J. Sayed, MD, UNC School of Medicine, said in a statement to The American Journal of Managed Care^®. “Response rates in this group are similar to those who haven't been exposed to prior biologic treatments and indicate that it is effective as both a first- or second-line treatment option based on provider and patient preferences."

References

1. Porter ML, Martorell A, Sayed CJ, et al. Povorcitinib in patients with moderate to severe hidradenitis suppurativa: 54-week efficacy and safety results from the STOP-HS1 & STOP-HS2 phase 3 studies. Presented at: 2026 AAD Annual Meeting; March 27-31, 2026; Denver, CO. Presentation 80034.
2. Sayed CJ, Martorell A, Porter ML et al. Povorcitinib for moderate-to-severe hidradenitis suppurativa: week 24 interim phase 3 results in anti-TNF-experienced patients. Presented at: 2026 AAD Annual Meeting; March 27-31, 2026; Denver, CO. Poster 75195.
3. Incyte announces new positive 54-week late-breaking data for povorcitinib in hidradenitis suppurativa at the 2026 American Academy of Dermatology (AAD) Annual Meeting. News release. Incyte. March 28, 2026. Accessed March 28, 2026. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-new-positive-54-week-late-breaking-data