The Janus kinase (JAK) inhibitor CTP-543 (Concert Pharmaceuticals) is effective for the treatment of moderate to severe alopecia areata, according to interim results from a phase 2a randomized safety and efficacy study (NCT03137381).
"We've identified our minimally effective dose," James Cassella, PhD, chief development officer at Concert, told Medscape Medical News.
The autoimmune disease affects about 650,000 people in the United States at any given time, and there is currently no approved treatment. CTP-543 is a modified version of ruxolitinib, a JAK inhibitor approved for the treatment of myelofibrosis and polycythemia vera.
Cassella presented interim results from 104 patients with moderate to severe alopecia areata who received twice-daily CTP-543 — 4 mg or 8 mg — or placebo for 24 weeks at the American Academy of Dermatology 2019 Annual Meeting in Washington, DC.
The primary end point — a 50% relative reduction in Severity of Alopecia Tool (SALT) score from baseline at 24 weeks — was met by significantly more patients in the 8 mg group than in the placebo group (47.0% vs 8.6%; P < .001).
In the 8 mg group, there was an even distribution of patients with patchy hair loss (the less-severe form of the condition), with alopecia totalis, and with alopecia universalis.
There was no significant difference in SALT score improvement between the 4 mg group and the placebo group.
No serious adverse events were reported in the interim results. The most common events were headache, cough, upper respiratory tract infection, acne, and nausea.
The remaining comparison of twice-daily CTP-543 12 mg and placebo is ongoing, but the team plans to start a phase 3 trial next year, Cassella told Medscape Medical News.
On March 6, the company announced that because these interim results show promise, it will begin an open-label trial to test whether a once-daily 16 mg dose of CTP-543 is as effective as a twice-daily 8 mg dose.
"That will obviously help adherence, would be important to the patient, and will help us determine not only the dose range that we want to bring into the phase 3 study, but also how we will dose in the phase 3 study," Cassella said.
Dermatologists are watching the development of JAK inhibitors closely because they could offer a systemic solution to a disease that can devastate patients, said Elizabeth Houshmand, MD, a dermatologist in private practice in Dallas.
Last year, two investigational oral drugs — PF-06651600, a JAK3 inhibitor, and PF-06700841, a JAK1 and tyrosine kinase 2 inhibitor, both developed by Pfizer — were shown to be safe and effective for patients with moderate to severe hair loss in 24-week interim findings from a phase 2 trial, as reported by Medscape Medical News.
The multifactorial causes of alopecia areata have made treatment elusive, but "I do think the JAK inhibitors are really wonderful, new hope for patients," she told Medscape Medical News.
The autoimmune disease is "affected by your genetic makeup in combination with factors and triggers for hair loss, such as stress or extremes of dieting," she explained.
"The inhibitors are treating the pathologic process that drives diseases, interrupting the process," said Houshmand, whereas other treatments aim to reduce inflammation in isolated areas.
JAK inhibitors are also showing promise in the treatment of vitiligo and atopic dermatitis, she added.
Cassella is chief development officer at Concert Pharmaceuticals. Houshmand has disclosed no relevant financial relationships.
American Academy of Dermatology (AAD) 2019 Annual Meeting. Presented March 2, 2019.
Follow Medscape Dermatology on Twitter @MedscapeDerm and Marcia Frellick @mfrellick
Medscape Medical News © 2019
Cite this: Another JAK Inhibitor Shows Promise for Alopecia Areata - Medscape - Mar 11, 2019.