Conference Coverage

Oral JAK1/2 inhibitor promising in alopecia areata



– In a phase 2, dose-ranging study, 78% of patients with long-standing moderate or severe alopecia areata rated their condition as “much improved” or “very much improved” after 24 weeks on the top dose of an investigational oral selective Janus kinase 1 and 2 (JAK1/2) inhibitor, compared with 21% of placebo-treated controls, James V. Cassella, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Dr. James V. Cassella, chief developmental officer at Concert Pharmaceuticals Bruce Jancin/MDedge News

Dr. James V. Cassella

The primary study endpoint – at least a 50% reduction in the Severity of Alopecia Tool (SALT) score between baseline and 24 weeks – was achieved in 58% of patients on the JAK1/2 inhibitor (known for now as CTP-543) at 12 mg twice a day, 47% of those on CTP-543 at 8 mg twice a day, 21% on 4 mg twice a day, and in 9% of controls on placebo in the double-blind randomized trial. The 4-mg twice-daily dosing will not move on to phase 3 studies because of its demonstrated lack of efficacy, according to Dr. Cassella, chief development officer at Concert Pharmaceuticals, the study sponsor.

The study included 149 adults whose current episode of alopecia areata was of 3-6 years’ duration, with an average lifetime 15-year history of active disease. Their average baseline score on the 0-100 SALT scale was in the upper 80s, indicative of 80% or greater hair loss.

A SALT 75 response, meaning at least a 75% reduction in SALT score from baseline, was achieved in a dose-dependent fashion: In 42% of patients at the top dose of CTP-543, 29% of those on 8 mg twice a day, 14% with 4 mg twice a day, and in 7% of controls. An even more rigorous SALT 90 response was attained in 36%, 16%, 2%, and no controls, respectively.

The 12-mg twice-daily dosing produced faster onset and greater magnitude of response than did the 8-mg twice-daily dosing, but this dose-ranging study is not the final word on that score, according to Dr. Cassella.

“Week 24 is not a magic number,” he said. “The slope of the efficacy line for 8 mg [twice a day] looked like it was still going up at week 24, and the 12-mg BID curve hadn’t completely plateaued. Those are things we will consider for the future in terms of long-term trials.”

Changes in the eyebrows and lashes weren’t formally assessed in this study, although they will be in future trials. Anecdotally, however, patients with alopecia areata at those sites typically experienced complete or nearly complete regrowth in response to the higher doses of CTP-543, he said.

Safety-wise, there was no trend for increased adverse events with increasing doses of CTP-543. The observed treatment side effects were those typical of JAK inhibitors as a class effect, mainly headache, nasopharyngitis, upper respiratory infections, and new-onset acne. In terms of hematologic findings of special interest, there was one case of reversible neutropenia in the control group and another in the 8-mg twice-daily group, which resolved upon temporary suspension of treatment.

“Nothing surprising to us, and nothing very serious,” Dr. Cassella said.

Most patients in the 12-mg twice daily group have enrolled in an ongoing long-term extension study. In addition, two phase 2 studies are ongoing, with a focus on once-daily versus twice-daily dosing at 8 mg or 12 mg. Phase 3 studies are in the planning stage, he added.

The phase 2 dose-ranging study was sponsored by Concert Pharmaceuticals.

CTP-543 is one of an array of oral JAK inhibitors now in the developmental pipeline for alopecia areata, a severe, psychosocially devastating disease for which at present there is no Food and Drug Administration–approved therapy.

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