Phase 2 Studies of Novel JAK1 Inhibitor for Hidradenitis Suppurativa Show Promise

Doug Brunk

January 24, 2022

Use of a novel oral Janus kinase 1 inhibitor known as INCB054707 by patients with moderate to severe hidradenitis suppurativa (HS) produced rapid and dose-dependent clinical responses, results from two small phase 2 studies showed.

"INCB054707 is an oral, small-molecule JAK1 inhibitor with approximately 52-fold greater selectivity for JAK1 versus JAK2," researchers led by Afsaneh Alavi, MD, of the Mayo Clinic in Rochester, Minn., wrote in an article published Jan. 2, 2022, in the British Journal of Dermatology. "Specifically targeting JAK1, a critical regulator of proinflammatory cytokine signaling implicated in several immune-related diseases, may reduce cytokine signaling involved in HS pathogenesis while limiting JAK2-mediated cytopenias."

For the first study, 10 patients received 15 mg INCB054707 once daily for 8 weeks (NCT03569371). For the second study, 35 patients were randomized to 30, 60, or 90 mg INCB054707 once daily or placebo (3:1 within each cohort) for 8 weeks (NCT03607487). Eligibility criteria for both studies included patients with Hurley stage II/III HS who aged 18-75 years with lesions present in two or more anatomic locations, and a total abscess and inflammatory nodule count of three or more. The primary endpoint for both studies was safety and tolerability. Secondary endpoints included HS Clinical Response (HiSCR) and other efficacy measures.

The researchers reported that 30% of patients in study 1 and 42.3% of patients who received INCB054707 in study 2 experienced one or more treatment-emergent adverse event, most commonly upper respiratory tract infection. Among evaluable patients, 3 patients (42.9%) in study 1 and 17 patients in study 2 (65.4%) achieved HiSCR at week 8, compared with 57.1% of those in the placebo group. By dosing, 55.6% in the 30-mg group achieved HiSCR at week 8, compared with 55.6% in the 60-mg group and 87.5% in the 90-mg group.

"In conclusion, safety and efficacy findings from these two phase 2 studies establish proof of concept for the JAK1 inhibitor INCB054707 in the treatment of moderate to severe HS," the authors wrote. "A phase 2, dose-ranging, placebo-controlled study exploring three dose levels and including approximately 200 patients is ongoing (NCT04476043) and expected to provide additional evidence of the safety and efficacy profile of INCB054707 in patients with HS."

INCB054707 is being developed by Incyte Corporation. Alavi disclosed that she has received honoraria as a consultant or advisory board participant from AbbVie, Janssen, Novartis, Boehringer Ingelheim, InflaRX, and UCB, and received honoraria as an investigator for Boehringer Ingelheim and Processa.

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