How Will Upadacitinib, Povorcitinib Benefit Hidradenitis Suppurativa?

As previously covered on HCPLive, hidradenitis suppurativa (HS) has been privy to some promising developments in recent years—namely, the introduction of interleukin 17 (IL-17) inhibitors like secukinumab and bimekizumab to the limited market for the chronic skin disease.¹ But investigators are far from done in bolstering the HS therapy toolbox.

In the second segment of an interview 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 the anticipated US Food and Drug Administration (FDA) marketing of upadacitinib and povorcitinib for the treatment of HS. The Janus kinase (JAK) inhibitors—that Hsiao previously said are approximately 1 - 2 years away from possibly reaching the US market—would provide patients with their first orally administered agent.

“And there are patients who are really needle-phobic, and it takes a long time to really convince them to give a biologic injectable a chance,” Hsiao said. “To be able to offer an oral medication that has good efficacy and good safety profile, I think it'd be a really big game-changer too, because the patients are already used to having taken antibiotics, or people are used to taking pills.”

While Hsiao and her colleagues are still awaiting published, pivotal phase 3 trial data for either upadacitinib or povorcitinib in patients with HS, she acknowledged a recent small cohort study conducted by John Frew, MBBS, MMed, MSc, PhD, et al that showed all patients who were initiated on daily upadacitinib 15 mg—switched to 30 mg if necessary by week 4—achieved 50% Hidradenitis Suppurativa Clinical Response (HiSCR50) by week 12.²

“I feel like what I'm hoping for is a fast onset of action, a good safety profile amongst our patients with HS—we have known cardiovascular comorbidities, for example—and the ability to offer something that's not just an injectable for long-term management of HS,” Hsiao said about JAK inhibitors.

Regarding the anticipated phase 3 findings for both JAK inhibitors, Hsiao expressed hope for data showing durable HS response, consistent safety outcomes beyond 1 year, and consistent efficacy profiles regardless of clinical characteristics from patient to patient.

One common thing is, if the patient is biologic-naive versus biologic-experienced—because now we have a cohort of patients who may have been on adalimumab for years because it was the only one that was FDA-approved—what does it look like for that patient who's switching in, versus someone who's never been on an agent before?” Hsiao said. “We would like to know that in the tougher-to-treat populations too, for example, that we can see good efficacy results.”

References

1. ^{Kunzmann K. Secukinumab and Bimekizumab for Hidradenitis Suppurativa. HCPLive. Published June 10, 2024. https://www.hcplive.com/view/secukinumab-bimekizumab-hidradenitis-suppurativa}
2. ^{Kozera E, Flora A, Frew JW. Real-world safety and clinical response of Janus kinase inhibitor upadacitinib in the treatment of hidradenitis suppurativa: A retrospective cohort study. J Am Acad Dermatol. 2022;87(6):1440-1442. doi:10.1016/j.jaad.2022.07.047}