New positive phase 3 data for povorcitinib in hidradenitis suppurativa

Dr Martina Porter highlights the encouraging 54-week efficacy and safety findings from the STOP-HS programme

Povorcitinib (INCB54707) is an oral, small-molecule selective Janus kinase (JAK) 1 inhibitor currently being evaluated in phase 3 clinical trials for adults with moderate-to-severe hidradenitis suppurativa (HS).

The phase 3 STOP-HS programme comprises two registrational studies, STOP-HS1 (NCT05620823) and STOP-HS2 (NCT05620836), which are designed to evaluate the efficacy and safety of povorcitinib in patients with HS. Interim 24-week findings from the programme have previously shown encouraging early results.

At the 2026 American Academy of Dermatology (AAD) Annual Meeting in Denver, CO, USA, a late-breaking oral presentation featured the 54-week results from the programme. To better understand what these data show and their potential clinical impact for the HS care, we spoke with Dr Martina Porter, STOP-HS study investigator, Assistant Professor of Dermatology at Harvard Medical School, and Vice Chair for Research and Academics in the Department of Dermatology at Beth Israel Deaconess Medical Center, Boston, MA, USA.

Abstract: Povorcitinib in Patients With Moderate to Severe Hidradenitis Suppurativa: 54-Week Efficacy and Safety Results From the STOP-HS1 & STOP-HS2 Phase 3 Studies’ was presented at AAD 2026, 27-31 March in Denver, CO, USA

TouchDERMATOLOGY coverage from AAD 2026:

Transcript:

What are the main limitations of current treatment options for hidradenitis suppurativa?

There are a couple of limitations. One is that we still have very few drugs available. Although more drugs have been developed recently, and they have made a major difference to patients’ lives and to our ability to treat this disease, they still have not reached the level we have seen in some other dermatologic conditions, such as psoriasis and atopic dermatitis. Those available are also very similar in their mechanisms of action.

The other limitation is that our clinical trials have focused only on moderate-to-severe HS, whereas the vast majority of our patients have mild-to-moderate disease. At present, we do not have any therapies approved for that indication.

What is povorcitinib, and how does it differ from existing treatments for hidradenitis suppurativa?

First and foremost, from the patient perspective, this treatment is an oral pill rather than an injection, which may be more appealing for some people.

The other difference is that, of the three drugs currently approved, one is a tumour necrosis factor (TNF)-alpha inhibitor and the other two are interleukin (IL)-17 inhibitors. Povorcitinib is a selective JAK1 inhibitor, so its mechanism does not directly block TNF-alpha or IL-17, and therefore works in a completely different way.

It is still not entirely clear how JAK inhibition works in HS, because we do not yet fully understand the pathogenesis of the disease. However, it is very appealing to have another treatment option, particularly because HS is highly heterogeneous in real-world practice, and it is unlikely that any single treatment will be effective for every type of disease.

What were the objectives and study designs of the phase 3 STOP-HS1 and STOP-HS2 trials?

These were the pivotal 54-week phase 3 trials of povorcitinib. The trial design involved patients being randomly assigned to receive placebo, povorcitinib 45 mg or povorcitinib 75 mg. After week 12, patients in the 75 mg group remained on 75 mg, and those in the 45 mg group remained on 45 mg, while those who had initially received placebo were re-randomized to one of the two active treatment groups. The data presented at the AAD 2026 meeting focused on the safety and efficacy results through week 54.

This trial enroled patients with moderate-to-severe disease, and they were not allowed to receive any antibiotics or other therapies for HS during the study, which differs somewhat from some of our previous trials. Overall, the patients in this study were very similar to those included in other phase 3 study programmes to date.

What were the efficacy findings?

Before looking at the 54-week efficacy and safety findings, it is important to note that this study population included several relevant baseline risk factors for a drug with this mechanism. Around half of the patients were smokers, the mean body mass index was 34, and more than 20% had a body mass index above 40. These are important considerations when assessing the safety of JAK inhibitors, particularly as there are often questions about whether this is an appropriate mechanism for this patient population.

The very good news was that, when the week 12 data were presented, around 40% of patients achieved HiSCR50 (Hidradenitis Suppurativa Clinical Response 50), compared with just under 30% in the placebo group. Looking out to week 54, and as is often seen in these trials, patients continued to improve over the following 6 to 12 months.

By week 54, up to 70% of patients in both trials had achieved HiSCR50. We also looked at greater depth of response, because that is important and is usually something that occurs over a longer period of time, rather than immediately within the first 12 to 16 weeks, given how inflammatory this disease is. By week 54, around half of patients had achieved HiSCR75, and about 20% had achieved HiSCR100, essentially meaning no inflammation, which I think is pretty impressive for a disease that can be so severe for patients.

What were the safety findings?

The safety profile was quite in line with what we see for other JAK inhibitors. As mentioned, patients with HS have more comorbidities than the average dermatology patient, although they may benefit somewhat from being a younger patient population overall.

Not surprisingly for this population, around 80% of patients in the trial had some type of adverse event over 54 weeks. This likely reflects the high burden of comorbidities at baseline. The most common adverse event was acne, seen in around 15–20% of patients, which is slightly higher than has been reported in other disease settings.

It probably makes sense mechanistically, since HS is a follicular occlusion disorder and acne falls within the same broad disease spectrum. Importantly, all cases were mild-to-moderate, so patients were not developing severe acne on the JAK inhibitors. There were also some cases of herpes zoster, but there were no differences between the two doses in terms of the adverse events observed.

What people are always curious about are the thromboembolic and MACE events. There was one patient who had a MACE event, a stroke, and then three patients total who had thromboembolic events in the STOP-HS2, and two in the STOP-HS1. That was about five patients out of over 1200 in the study. They do appear still to experience thromboembolic events. However, given the background risk profile of this patient population, the rates were relatively low, which is reassuring.

What is the clinical significance of these findings for hidradenitis suppurativa management?

I have been using JAK inhibitors in clinical practice for many years, and I have seen patients who had previously tried multiple biologics without any response go on a JAK inhibitor and experience a dramatic improvement.

Another abstract presented at the conference, although not part of the late-breaking session, looked specifically at patients who had already been exposed to biologics, and their efficacy rates with povorcitinib were broadly similar. Interestingly, and perhaps not surprisingly, those patients had much more severe disease at baseline.

Taken together, these findings suggest that there may be some patients for whom JAK inhibitors are more effective than biologics, which would ultimately give us more options and allow us to treat patients more effectively. This study did not assess that directly. However, I think that, in the longer term, some of our more severe patients will likely require dual therapy with a biologic and potentially a JAK inhibitor. Having multiple mechanisms available in that setting really does make sense.

What questions remain unanswered?

I think the interesting question for all of these studies is what happens once we move into the real-world setting, because there are clearly some patients who do much better with different mechanisms of action. That is not something we can fully capture in a trial like this.

In my clinical practice, JAK inhibitors seem to work particularly well for patients with very severe disease, especially those with extensive tunnelling in the buttocks and groin, somewhat resembling a Crohn’s disease phenotype, which may make sense given that these agents are also approved for inflammatory bowel disease. They also seem to work very well in patients with a high burden of nodules, but who have not yet progressed to these more severe phenotypes.

Interestingly, another JAK inhibitor, topical ruxolitinib cream, was studied in a trial that included a similar patient population, but with substantially fewer lesions. Over time, I think we will begin to tease out where these drugs work best and which patients are most likely to benefit. Hopefully, further analyses, including post-hoc analyzes, will help support that.

One additional point that is important to mention is quality of life, which is often what matters most to patients. We often focus on efficacy, but we also saw very meaningful improvements in skin pain, fatigue, quality of life and the ability to carry out daily activities.

That is something I think we really need to emphasize when discussing these medications with patients, namely the broader impact they can have. It is also important to help set expectations, because this is not a treatment that necessarily works fully within 12 to 16 weeks; it may take a little longer to achieve the level of improvement patients are hoping for.

Cite: Positive 54-week data for povorcitinib in hidradenitis suppurativa. TouchDERMATOLOGY. 16 April, 2026

Editors: Gina Furnival

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