New Phase 3 Findings Demonstrate Efficacy of Povorcitinib for HS Treatment
These pivotal phase 3 data on povorcitinib were the results of the STOP-HS clinical trial, with results suggesting both efficacy and safety for hidradenitis suppurativa.
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In newly-announced findings released by Incyte, positive topline results for povorcitinib were highlighted from the pivotal phase 3 STOP-HS clinical study assessing the oral small-molecule JAK1 inhibitor’s safety and efficacy in adults aged ≥18 years with moderate to severe hidradenitis suppurativa (HS).1
Povorcitinib is a medication currently in phase 3 trials for different dermatologic conditions such as HS, vitiligo, and prurigo nodularis, and its phase 2 results have been previously reported by HCPLive.2 In the STOP-HS trial program, a pair of phase 3 studies titled STOP-HS1 (NCT05620823) and STOP-HS2 (NCT05620836) were conducted to evaluate povorcitinib’s use among adults with moderate to severe HS.
"HS is a challenging and debilitating condition without a cure. Given the limitations of current HS treatments and its 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, MD, Incyte’s chief medical officer, said in a statement. "The positive Phase 3 data highlights the potential of povorcitinib as an effective oral treatment option for people living with HS.”1
HS is a chronic inflammatory skin condition that is known for a variety of symptoms, including abscesses and painful nodules that can irreversibly damage tissue, lead to permanent scarring, and severely diminish patients’ overall quality of life. The debilitating disease’s pathogenesis and progression are believed to be driven by the over-activity of the JAK/STAT signaling pathway and its impact on inflammation.
Povorcitinib, as a JAK1 inhibitor, would potentially address HS and was consequently evaluated in the recent STOP-HS trial program. In STOP-HS1 and STOP-HS2, the studies involved a 12-week, placebo-controlled, double-blind treatment phase, after which a 42-week extension period and a 30-day safety follow-up period were conducted by investigators.
Approximately 600 individuals participated in the studies who had a confirmed HS diagnosis for a minimum of 3 months before screening. The investigative team’s primary endpoint during both analyses was the proportion of subjects attaining a Hidradenitis Suppurativa Clinical Response 50 (HiSCR50) at the 12-week mark, defined by the team as a 50% reduction at least in subjects’ total abscess and inflammatory nodule count (AN count) from the point of baseline without a rise in abscess or draining tunnels.
The investigators also assessed a variety of key secondary endpoints, including the percentage of participants reporting at least a single HS flare-up in the 12 weeks and the proportion of subjects attaining a 75% reduction in AN count (HiSCR75) by the 12-week mark. The team also examined the frequency and severity of adverse events among patients.
Overall, STOP-HS1 and STOP-HS2 met their primary endpoints at the 45 mg and 75 mg doses of povorcitinib, which suggested a statistically significant improvement in HiSCR50 scores compared to those in the placebo arm of the studies.
In STOP-HS1, the proportion of those on 45 mg povorcitinib doses achieving HiSCR50 at Week 12 was 40.2% versus 29.7% for those in the placebo arm (P = .024). Among those given 75 mg, 40.6% achieved HiSCR50 versus 29.7% on placebo (P = .022).
During the STOP-HS2 study, 42.3% of those in the 45 mg povorcitinib cohort achieved HiSCR50 versus 28.6% on placebo (P =.004). In the 75 mg arm, 42.3% versus 28.6% achieved this score, respectively (P = .003).
The investigators concluded that povorcitinib, among a predefined subgroup of participants with prior biologic exposure, demonstrated a greater efficacy differential as opposed to placebo. Specifically, in STOP-HS1, the 45 mg group saw a response of 34.2% versus 21.9% on placebo (P = .096) and a rate of 37.8% versus 21.9% in the 75 mg group, respectively (P = .037).
In the STOP-HS2 study, rates in the 45 mg group were 45.0% in the treatment arm versus 19.5% for the placebo arm (P = .001) as well as 40.0% versus 19.5% in the 75 mg group, respectively (P = .005). The team also found that their 12-week results indicated that subjects given povorcitinib demonstrated deeper clinical responses, highlighting such results as a reduction in HS flare frequency, an increased proportion of such patients attaining HiSCR75, and a >3-point decrease in Skin Pain NRS.
Investigators further noted that the medication exhibited a rapid onset of action, highlighting such results as a notably early reduction in patients’ reports of skin pain. The drug’s overall safety profile was also shown to have remained consistent with prior data, with no new safety signals pointed out and with both dosage levels being well-tolerated.
Incyte’s findings, overall, were noted to support the planned global regulatory submission for povorcitinib as a medication for HS.1
References
Incyte Announces Positive Topline Results From Two Phase 3 Clinical Trials of Povorcitinib in Patients With Hidradenitis Suppurativa. Incyte. March 17, 2025. https://investor.incyte.com/news-releases/news-release-details/incyte-announces-positive-topline-results-two-phase-3-clinical.
Smith T. Phase 2 Trial For Povorcitinib Sees Positive Trend In Hidradenitis Suppurativa Treatment. HCPLive. September 12, 2022. https://www.hcplive.com/view/phase-2-trial-povorcitinib-positive-trend-hidradenitis-suppurativa-treatment. Date accessed: March 17, 2025.
