Oral selective JAK1 inhibitor a win in hidradenitis suppurativa

INCB054707, an oral Janus kinase (JAK)1 inhibitor, shows promise in the treatment of moderate-to-severe hidradenitis suppurativa (HS), reducing the abscess and inflammatory nodule (AN) count in addition to having an acceptable safety profile, according to data from two phase II trials.

“Local and systemic inflammation in HS is driven in large part by JAK-mediated cytokines, including interleukin (IL)-6, IL-17, and interferons,” said Dr Afsaneh Alavi from Mayo Clinic in Rochester, Minnesota, US, who presented the results during the 29th European Academy of Dermatology and Venereology (EADV) Virtual Congress.

Meanwhile, the investigational drug is a small molecule JAK inhibitor with about 52-fold greater selectivity for JAK1 vs JAK2, Alavi added.

In the first study, 10 patients (mean age, 40.7 years; 30 percent female; 60 percent white) received INCB054707 (15 mg) once daily for 8 weeks. The second study, on the other hand, randomly assigned 35 patients (mean age, 41.5 years; 80 percent female; 89 percent white) to groups given once-daily treatment with INCB054707 30 mg (n=9), 60 mg (n=9), or 90 mg (n=8), or placebo (n=9) for 8 weeks. Both studies included a 30-day safety follow-up period. [EADV 2020, abstract 2665]

At baseline, all patients had lesions present in more than two anatomic locations (Hurley stage II or III). The mean AN count was 7.3 in study 1 and between 11.2 and 17.1 in study 2.

“INCB054707 was well tolerated,” Alavi noted. “Only one patient across both studies discontinued treatment because of treatment-emergent adverse events (TEAEs),” specifically grade 3 thrombocytopenia, which occurred at the highest dose (90 mg).

Overall, 70 percent of patients in study 1 had at least one grade mild-to-moderate TEAE, while 30 percent developed treatment-related adverse events (TRAEs). In study 2, 81 percent of patients receiving the investigational drug had TEAEs (12 percent grade 3, all thrombocytopenia at 90 mg), whereas 42 percent experienced TRAEs.

Based on the 8-week efficacy results, three patients (43 percent) in study 1 showed clinical response. In study 2, 17 patients (30 mg, 56 percent; 60 mg, 56 percent; 90 mg, 88 percent) in the INCB054707 groups and four patients (57 percent) in the placebo group achieved the same.

“Improvements in AN count were seen as early as week 1 with INCB054707 and were maintained over the treatment period,” Alavi said.

The proportions of patients achieving an AN count of 0–2 at weeks 8 and 12 were 43 percent and 57 percent, respectively, in study 1, and 50 percent (30 mg, 44 percent; 60 mg, 44 percent; 90 mg, 63 percent vs 57 percent with placebo) and 28 percent (30 mg, 33 percent; 60 mg, 0 percent; 90 mg, 57 percent vs 14 percent with PBO) in study 2.

“[Finally], treatment with INCB054707 was associated with dose-dependent modulation of circulating inflammatory mediators,” according to Alavi, adding that a deeper analysis regarding this effect is ongoing.

Given the encouraging data, additional clinical studies of JAK1 inhibition for HS are warranted, she said.