Incyte has announced positive topline results from its pivotal Phase 3 STOP-HS clinical trial program evaluating povorcitinib (INCB054707), an oral small-molecule JAK1 inhibitor, in adult patients with moderate to severe hidradenitis suppurativa (HS). The data show statistically significant efficacy at both tested doses with a favorable safety profile, potentially offering a new oral treatment option for this debilitating inflammatory skin condition.
Both the STOP-HS1 and STOP-HS2 studies met their primary endpoint, with a significantly higher proportion of patients treated with povorcitinib achieving Hidradenitis Suppurativa Clinical Response (HiSCR50) compared to placebo at Week 12. HiSCR50 is defined as at least a 50% reduction from baseline in total abscess and inflammatory nodule count, with no increase in abscess or draining tunnel count.
Significant Clinical Response Across Both Studies
In the STOP-HS1 trial, 40.2% of patients receiving the 45 mg dose and 40.6% of those on the 75 mg dose achieved HiSCR50, compared to 29.7% on placebo (p=0.024 and p=0.022, respectively). Similar results were observed in the STOP-HS2 trial, with 42.3% of patients in both dose groups achieving HiSCR50 versus 28.6% on placebo (p=0.004 and p=0.003, respectively).
Notably, povorcitinib demonstrated even greater efficacy in patients previously exposed to biologics, a population that often has limited treatment options. In STOP-HS2, 45.0% of biologic-experienced patients on the 45 mg dose achieved HiSCR50 compared to just 19.5% on placebo (p=0.001), while 40.0% on the 75 mg dose reached this threshold (p=0.005).
"These results are particularly encouraging for patients who have failed previous biologic therapies," said Steven Stein, M.D., Chief Medical Officer at Incyte. "The significant response rates in this difficult-to-treat population highlight povorcitinib's potential to address an important unmet need in HS management."
Comprehensive Efficacy Profile
Beyond the primary endpoint, povorcitinib demonstrated efficacy across multiple secondary measures. At Week 12, a greater proportion of treated patients achieved deeper clinical responses (HiSCR75), experienced fewer disease flares, and reported significant reductions in skin pain as measured by the Numeric Rating Scale (NRS).
The drug also showed a rapid onset of action, with meaningful improvements in skin pain occurring early in the treatment course. This is particularly relevant for HS patients, as pain is often cited as one of the most debilitating aspects of the condition.
Safety and Tolerability
The overall safety profile of povorcitinib was consistent with previous clinical data, with no new safety signals observed. Both the 45 mg and 75 mg doses were well tolerated throughout the 12-week treatment period.
This favorable safety profile is crucial for a condition requiring long-term management and supports povorcitinib's potential as a chronic treatment option for HS patients.
About Hidradenitis Suppurativa
Hidradenitis suppurativa is a chronic inflammatory skin condition affecting approximately 150,000 moderate to severe patients in the United States alone. The disease is characterized by painful nodules and abscesses that can lead to irreversible tissue destruction and scarring, significantly impacting patients' quality of life.
Current treatment options for HS are limited, with many patients experiencing inadequate response to available therapies. Over-activity of the JAK/STAT signaling pathway is believed to drive the inflammation involved in HS pathogenesis, making JAK inhibition a promising therapeutic approach.
Study Design and Population
The STOP-HS clinical trial program included two Phase 3 studies (STOP-HS1 and STOP-HS2) that each enrolled approximately 600 adult patients with moderate to severe HS. Participants had to have a total abscess and inflammatory nodule count of at least 5, lesions in at least two distinct anatomical areas, and a documented history of inadequate response to conventional systemic therapy.
Both studies featured a 12-week double-blind, placebo-controlled treatment period, followed by a 42-week extension period and 30-day safety follow-up. The primary endpoint was the proportion of patients achieving HiSCR50 at Week 12.
Regulatory Implications and Future Directions
Based on these positive results, Incyte plans to submit povorcitinib for regulatory approval for the treatment of HS worldwide. If approved, povorcitinib would be the first oral targeted therapy specifically indicated for HS, potentially transforming the treatment landscape for this challenging condition.
"Hidradenitis suppurativa is a challenging and debilitating condition without a cure," Dr. Stein emphasized. "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."
Incyte has indicated that detailed data from both STOP-HS studies will be submitted for presentation at upcoming scientific meetings, providing the medical community with a more comprehensive understanding of povorcitinib's efficacy and safety profile.
Beyond HS, povorcitinib is currently being evaluated in Phase 3 clinical trials for vitiligo and prurigo nodularis, as well as Phase 2 trials for asthma and chronic spontaneous urticaria, highlighting its potential across multiple inflammatory conditions with significant unmet needs.
