Unmet Needs in HS and Emerging Oral Options, With Martina Porter, MD

Povorcitinib, an oral selective JAK1 inhibitor, met its primary endpoint in the 2 randomized, double-blind, placebo-controlled phase 3 STOP-HS trials of 1,227 patients with moderate to severe hidradenitis suppurativa (HS).¹ At week 12, HiSCR50 rates were 40% (82/204) and 41% (82/202) with 45 mg and 75 mg in STOP-HS1 versus 30% (60/202) with placebo.¹ In STOP-HS2, HiSCR50 rates were 42% (88/208) for both doses versus 29% (58/203) with placebo.¹

Martina Porter, MD, is a dermatologist at Beth Israel Deaconess Medical Center in Boston and vice chair of research and academics in its department of dermatology. She specializes in HS care and clinical trials and is first author of the STOP-HS report published in Nature Medicine in August 2026.¹

Through week 54, HiSCR50 reached up to 71.4%, HiSCR75 up to 57%, and HiSCR100 up to 29%, according to Incyte.² Draining tunnels fell by up to 62.0% and abscesses by up to 63.7% with the 75 mg dose at week 54.² Treatment-emergent adverse events occurred in 76.2% to 83.4% of patients, with acne, nasopharyngitis, and upper respiratory tract infections most frequent, and serious events in 3.7% to 6.4%.²

Incyte has submitted a New Drug Application to the FDA and a Marketing Authorization Application to the EMA, and both are under review.² If approved, povorcitinib would add a mechanism distinct from the TNF alpha and IL-17 inhibitors used in HS today. In the following interview, Porter discusses unmet needs in HS, how response builds over time, which patients may benefit most, and the safety of oral JAK1 inhibition.

HCPLive: How does an oral JAK1 inhibitor add to a treatment landscape of injectable biologics for HS?

Martina Porter, MD: It's been interesting to see how HS has evolved in terms of our research pursuits in the last few years. We're very fortunate to have so many drugs that have gone through phase 3 studies and even been approved in the last couple of years. Adalimumab has been available for over 10 years now for HS, and it was our first and only drug, a TNF alpha inhibitor. In the last 2 years, we've had secukinumab and bimekizumab approved for HS, and I think that really revolutionized the field by giving us more options. It's amazing that we're going to have a totally different mechanism and also administration route for patients.

Povorcitinib is an oral selective JAK1 inhibitor. It's not approved for anything else yet, but it has been looked at in other conditions in dermatology. The very exciting part is not so much that it's oral, it's that it offers a totally different option for patients. TNF alpha and IL-17 are relatively close in the signaling pathway, and JAK inhibition in the JAK-STAT pathway doesn't overlap with TNF or IL-17 to the same degree. It may inhibit some of those molecules downstream, but it's not directly in line, so we're looking at being able to offer a totally different mechanism. For some patients who have already taken biologics and had very minimal response, this could be very promising. I've also seen in clinical practice that it has varying effects on different types of HS patients, so I also think it could be considered first line in the future, depending on how it's approved by the FDA.

HCPLive: Is it time to raise the bar for what counts as a successful treatment response in HS?

Martina Porter, MD: I think the answer overall is yes, with a lot of caveats to go along with it. The most important thing for patients is that when they start taking a medication, they notice something improving relatively soon, which keeps them motivated to stay on therapy. Seeing patients hit HiSCR50 as early as week 3 matters to them. I always say in clinical practice that HiSCR75, or approximately a 75% improvement, is what allows patients to take a therapy and say they're happy enough and want to continue. That's been supported by some of our patient-reported outcomes, where we see pretty stark differences between patients who get 75% better and those who do not. That's what I personally try to shoot for in clinical practice, but obviously the best outcomes for patients would be HiSCR90 and HiSCR100. Across all medications and all trials, though, it's very hard to hit those marks. It's not like psoriasis drugs, where we get PASI 75, 90, and 100 in more than half of patients in less than 4 months.

Even though HiSCR50 is our primary endpoint at week 12, HS is such an inflammatory and long-standing chronic disease that with most medications we see even more patients hit HiSCR50 at the 24-week mark, and again at 54 weeks. I always tell patients and other people treating HS that it's more of a marathon than a sprint. It requires a lot of patience on all of our parts, patients and clinicians, to wait to see these improvements. Improvement at week 3 and week 12 is important, but the maximum efficacy for most of these drugs lies 24 to 54 weeks down the line, and long-term data from other trials now show patients can still improve out to the 2- and 3-year marks. For milder patients we'll see improvements much sooner, but for patients with long-standing disease it takes a lot more time, so we don't want to give up too soon.

HCPLive: Which patients do you expect to benefit most from povorcitinib, including those who have already taken biologics?

Martina Porter, MD: At one of the recent conferences, they did an analysis of patients who were biologic-exposed prior to entering the trial to see what their efficacy endpoints were. The patients who had previously failed or stopped biologics for whatever reason did just as well as patients overall in the trial. That might sound like a throwaway, but it's a big difference, because those patients had much higher lesion counts and worse disease at baseline, with higher abscess, nodule, and draining tunnel counts, and they were still able to achieve the same types of endpoints as a patient who had never taken a biologic.

By the time this drug comes to market, quite a few of our patients will have already taken biologics, so it's important to know how this population does. To me, it suggests a really good treatment option for patients who may have already failed one of these biologics, because TNF alpha and IL-17 inhibitors are not that far apart in the pathophysiology they're targeting, whereas JAK inhibitors, specifically JAK1 selective, target different pathways. It also supports the idea that there are different drivers of disease for different patients, and some who didn't respond to traditional biologics may not have had disease signaling through TNF alpha or IL-17. For treatment-refractory patients, it also potentially opens the door to combining therapies, since JAK1 selective and IL-17A, for example, have very little overlap, and you may be able to hit both if you're able to get them approved.

I've used quite a few of the JAK inhibitors already approved for other conditions, and I've noticed something that isn't the type of data we capture in clinical trials: I think 2 populations really benefit from JAK inhibitors in HS. One looks very similar to the Crohn's patients we see with horrible tunneling or lots of fistulas in the groin and buttocks, the patients who sit down on the bed and there's pus everywhere. Those patients do pretty well on high-dose JAK inhibition, and it may be that they're more of a Crohn's phenotype, which also has many JAK inhibitors approved. On the complete opposite end of the spectrum are people with a lot of nodules who don't really make tunnels over time. They have a very long-standing history of disease, and maybe lots of females in their family have a similar presentation.

Those patients also do really well with JAK inhibition, but they're probably not the patients people automatically think need systemic therapy, because they're milder. I do think it'll be important as we move forward to start treating earlier, before people get scarring and tunneling, and maybe this medication will have a big impact in what we now call the window of opportunity to halt their disease before it gets worse.

HCPLive: Acne was the most common treatment-emergent adverse event. How did patients tolerate it, and how should dermatologists counsel and manage it?

Martina Porter, MD: Acne was the most common treatment-emergent adverse event in this trial, affecting just under 20% of patients overall. The interesting part was there was no dose-related issue. We thought maybe at the 12-week mark the higher dose had higher rates of acne, but when you look out to 54 weeks, the 2 groups had about the same number of patients with acne. They graded the severity of acne for this trial, and it's nice to be a dermatologist doing a clinical trial because we know we can trust the severity assessments for a skin condition. Almost all patients were mild, with a few moderate, and no one developed large cystic or severe acne reactions requiring discontinuation of the drug. Acne and HS also overlap a lot in treatment.

In clinical practice, for a patient with persistent acne, we might start with topicals and then transition to oral antibiotics or isotretinoin. In HS clinical trials, though, all of those medications can potentially affect the HS efficacy endpoints, so they're prohibited, and patients weren't able to receive full acne treatment. It's difficult to know what would have happened if we had been able to treat them adequately, which we'll be able to do in real practice. My personal experience is that JAK inhibitors cause acne across all populations, whether patients take them for atopic dermatitis, alopecia areata, or inflammatory bowel disease, and the patterns are very similar: mostly milder lesions in a hormonal distribution. HS mostly affects younger females, who are much more likely to get hormonal acne, so it wasn't surprising to see more acne in this population than in others.

This is the first very large phase 3 trial we've finished for JAK inhibitors in HS, so I think we're seeing a combination of the medication causing acne, which isn't unexpected for a JAK inhibitor, and a patient population at much higher risk of getting acne. I've been very successful in my clinical practice treating patients with the same acne paradigm we use for patients who don't have HS and aren't on JAK inhibitors.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools. Disclosures for Porter include AbbVie, Almirall, Arcutis, Aristea Therapeutics, Avalo Therapeutics, Eli Lilly, Incyte, Janssen, Merck, MoonLake Immunotherapeutics, Navigator Biosciences, Novartis, Pfizer, Sanofi, Sonoma Biotherapeutics, UCB and Zura Bio, and others.

REFERENCES:

1. Porter ML, et al. Povorcitinib for hidradenitis suppurativa: the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials. Nat Med. 2026;32(8):3071-3081. doi:10.1038/s41591-026-04534-z

2. Incyte. Incyte announces new positive 54-week late-breaking data for povorcitinib in hidradenitis suppurativa at the 2026 American Academy of Dermatology (AAD) Annual Meeting. Published March 28, 2026. Accessed November 9, 2026. https://www.businesswire.com/news/home/20260328441699/en/incyte-announces-new-positive-54-week-late-breaking-data-for-povorcitinib-in-hidradenitis-suppurativa-at-the-2026-american-academy-of-dermatology-aad-annual-meeting/