Povorcitinib Efficacy Holds in Biologic-Experienced HS, With Martina Porter, MD

Oral povorcitinib demonstrated sustained and deepening clinical response through 54 weeks in moderate-to-severe hidradenitis suppurativa (HS), with a biologic-experienced subgroup comprising nearly 40% of enrolled patients achieving efficacy rates comparable to those without prior biologic exposure.

Martina L. Porter, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, presented the 54-week STOP-HS extension data as a late-breaking abstract at the 2026 American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colorado, from March 27-31.

The STOP-HS extension follows up the STOP-HS1 (NCT05620823) and STOP-HS2 (NCT05620836), identically designed global phase 3 trials with a combined enrollment of 1,227 adults with moderate-to-severe HS (STOP-HS1, n = 608; STOP-HS2, n = 619), randomized 1:1:1 to povorcitinib 75 mg once daily, 45 mg once daily, or placebo for a 12-week placebo-controlled period, followed by a 42-week blinded extension through week 54. Enrollment required abscess and nodule (AN) count ≥5 in ≥2 anatomic areas, Hurley Stage II or III disease, duration ≥3 months, and prior systemic therapy. Mean disease duration was 10.3 years (SD, 9.4), mean AN count was 12.0 (SD, 8.8), and 75.5% had at least 1 draining tunnel at baseline. Biologic-experienced patients — those with prior exposure to a TNF-α or IL-17 inhibitor — comprised 37.2% of the trial population, a proportion Porter noted is substantially higher than in prior phase 3 HS programs.

At the primary endpoint of HiSCR50 at week 12, both doses achieved statistical significance versus placebo in both studies — 40.2% (45 mg) and 40.6% (75 mg) versus 29.7% for placebo in STOP-HS1 (P <.025), and 42.3% for both doses versus 28.6% for placebo in STOP-HS2 (P <.01). Response continued to deepen through the blinded extension, with HiSCR50 reaching 60.2% to 61.9% in STOP-HS1 and 57.3% to 67.5% in STOP-HS2 by week 54 in patients on continuous povorcitinib, and placebo-crossover patients achieving comparable rates after switching at week 12. High-threshold responses accumulated substantially over time: up to 29.0% of patients achieved HiSCR100 at week 54, and complete clearance of all inflammatory lesions (ANdT = 0) was documented in 16.1% to 20.2% of patients across both studies.

In a conversation with HCPLive at the meeting, Porter characterized the new data as clinically important in a disease where mechanistic heterogeneity likely determines which patients succeed on which treatments. Porter framed the deepening responses as a recalibration of what clinicians should expect from HS therapy — response at the 12- to 16-week placebo-controlled primary endpoint represents an early signal, not a treatment ceiling, and 6 to 12 months of continued therapy may be required before patients reach their maximal benefit.

A separate subgroup analysis presented at the same meeting examined efficacy in the biologic-experienced cohort specifically. These patients carried greater baseline disease burden — higher AN counts and more draining tunnels — consistent with a more refractory disease phenotype. Despite this, their HiSCR response rates at both week 12 and week 54 were comparable to those seen in the overall trial population, a result Porter described as mechanistically explanatory: patients who failed TNF-α or IL-17 inhibitors may not have been signaling disease primarily through those pathways, and JAK1 inhibition via the JAK-STAT axis represents a genuinely distinct mechanism capable of capturing response in that population. She noted this pattern is consistent with her clinical experience. The depth-of-response data further support this picture: by week 54, up to approximately 20% of patients achieved near-complete or complete inflammatory clearance, a threshold more familiar from psoriasis and atopic dermatitis than historically from HS. Patient-reported outcomes at week 54 reflected the clinical gains, with ≥3-point decreases in skin pain NRS achieved in 40.5% to 58.0% of eligible patients and ≥4-point improvements in DLQI in 59.4% to 64.7%.

Safety through week 54 was consistent with the established class profile of JAK1 inhibitors. The most common treatment-emergent adverse events were acne (16.4%–21.1%), nasopharyngitis (9.4%–13.6%), and upper respiratory tract infection (9.1%–12.2%). Serious treatment-emergent adverse events occurred in 3.7% to 6.4% of patients across arms; no malignancies excluding non-melanoma skin cancer were reported and MACE was observed in 1 patient (0.3%) in STOP-HS2.

“I think our mentality or mindset about treating patients has really shifted to where we're not expecting them to respond to therapies like our psoriasis patients do, or even our atopic dermatitis patients, this is a very different disease, but the data is very reassuring in terms of the efficacy,” Porter said.

Relevant disclosures for Porter include Abbvie, Bristol Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, UCB, Trifecta Clinical, Incyte, and Anaptys Bio.

References

1. Porter ML, et al. Povorcitinib in moderate-to-severe hidradenitis suppurativa: 54-week results from the phase 3 STOP-HS1 and STOP-HS2 trials. Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.

2. Porter ML, et al. Povorcitinib efficacy in biologic-experienced patients with moderate-to-severe hidradenitis suppurativa: subgroup analysis from STOP-HS1 and STOP-HS2. Presented at: AAD Annual Meeting; Denver, Colorado; March 27-31, 2026.