Therapies in Development for Hidradenitis Suppurativa

As previously reviewed on HCPLive, the previously dormant market for hidradenitis suppurativa (HS) therapies presented a burden for clinicians seeking to provide patient relieve and symptom resolution for the burdensome, chronic skin disease. Only now, agents from the interleukin 17 (IL-17) and Janus kinase (JAK) inhibitor drug classes have reached late-stage assessment and provide a robust armamentarium for dermatologists.¹

And the toolbox is only growing, explained one expert.

In the final segment of an interview with HCPLive during the Society for Dermatology Physician Assistants (SDPA) 2024 Summer Meeting, Jennifer L. Hsiao, MD, clinical associate professor at the Keck School of Medicine of USC, discussed promising drugs in earlier development to treat HS. Among those highlighted included innate immune system pathway-targeting drugs—options from the IL-1 alpha and beta inhibitor class like lutikizumab, as well as IL-36 inhibitors previously indicated to treat general pustular psoriasis (GPP).

“But with HS also having that neutrophilic innate immune component, (we’re) seeing if basically moving into phase 2b/3 trials to see if there can be efficacy there,” Hsiao said. “There's also a CXCR 1 and CXCR 2 inhibitor—also targeting that innate immune system activation pathway. So, I think because we don't know the exact pathophysiology of HS and which pathways carry more weight, and whether that varies in different individuals, it makes sense to me to explore different pathways and see if we can find something.”

Additionally, oral BTK inhibitor remibrutinib was recently shown to have significant promise to treat HS based on phase 2 data presented at the American Academy of Dermatology (AAD) 2024 Annual Meeting earlier this year, and it also shows benefit for patients with chronic urticaria.²

“I think BTK inhibitors, being like a small molecule inhibitor for intracellular signaling blocking, is going to be a class of medications that dermatologist are going to see more and more of—just because there's going to be different indications that these types of medications are going to be approved for,” Hsiao said.

Hsiao explained there are still pertinent questions about the interplay of these investigative therapies with the disease itself: should therapies target upstream or downstream? What are the relative adverse event risks? Does variation in disease progression alter strategy? Does benefit with a BTK inhibitor implicate a role of B cells in disease pathophysiology?

“There's a lot of unknown questions surrounding pathophysiology, and I'm just excited that we have these different therapeutic targets that are being explored,” Hsiao said.

Even with a rapidly growing market of potential HS therapies, clinicians face challenges with delays to diagnoses and a dearth of resources to inform timely, refined treatment strategies. It’s a field “ripe for research” in a number of ways, Hsiao said.

“I do think that the approach we have now with a robust pipeline is great, but certainly digging into that basic science and being able to figure out more—what might be contributing more, or maybe is there something that a stone we haven't uncovered yet—I think that's something that I'm very interested to know,” she said.

References

1. ^{Kunzmann K. How Will Upadacitinib, Povorcitinib Benefit Hidradenitis Suppurativa? HCPLive. Published June 11, 2024. https://www.hcplive.com/view/how-will-upadacitinib-povorcitinib-benefit-hidradenitis-suppurativa}
2. ^{Kimball AB. Efficacy and safety of the oral Brutons tyrosine kinase inhibitor, remibrutinib, in patients with moderate to severe hidradenitis suppurativa in a randomized, phase 2, double-blind, placebo-controlled trial. Paper presented at: American Academy of Dermatology (AAD) 2024 Annual Meeting. March 8 – 12, 2024. San Diego, CA.}