Novel JAK1/2 inhibitor shows remarkable efficacy in alopecia areata

The Janus kinase (JAK) inhibitor CTP-543 showed promising results in patients with moderate-to-severe alopecia areata according to interim results from a phase 2a study [1].

Alopecia areata is a poorly treatable autoimmune disease that affects women, men, and children of all ages. This chronic condition has a remarkable negative impact on quality of life and is associated with anxiety, depression, and other autoimmune conditions.

CTP-543 inhibits both JAK1 and JAK2 and is a modified version of the JAK inhibitor ruxolitinib, currently approved for the treatment of myelofibrosis and polycythemia vera. The double-blind, randomised, placebo-controlled, dose-ranging, phase 2 trial included 149 adult patients with moderate-to-severe alopecia areata. The entry criterion was an at least 50% hair loss as measured by Severity of Alopecia Tool (SALT) score. Patients were randomised to receive 4, 8, or 12 mg CTP-543 or placebo twice daily. Primary efficacy endpoint was a 50% relative reduction in the SALT score from baseline to 24 weeks. Dr James Cassella, chief development officer at Concert Pharmaceuticals (USA), also presented additional clinical endpoints, including the percentage of patients achieving 75% and 90% relative change in SALT at week 24 from baseline and a patient global impression of improvement.

Significantly more patients in the 12 mg and 8 mg group achieved the primary endpoint at week 24 than in the placebo group (47% vs 58%, respectively, compared with 8.6% in the placebo group; both doses P<0.001 vs placebo). The reduction in SALT score in the 4 mg group was not statistically significant compared with placebo. A significant difference compared with placebo was seen after 12 weeks with the 12 mg dosage and after 16 weeks with the 8 mg dosage, but there was still a steep increase of response until week 24. The 12 mg dose was particularly effective: 42% of patients treated with this regimen gained a ≥ 75% change in SALT relative to baseline, 36% a ≥ 90% change in SALT (both comparisons P<0.001 vs baseline). At week 24, 78% of patients treated with 12 mg and 58% of patients treated with 8 mg rated the disease as “much improved” or “very much approved” (both comparisons P<0.001 vs placebo). “We also saw a very good treatment effect on eyebrow and eyelash growth,” said Dr Cassella.

The 12 mg dose was numerically superior and produced a faster onset and greater magnitude of effect compared with 8 mg. Generally, therapy with the novel JAK inhibitor was well tolerated. “There were no real signs of any increase, in particular no differences in grade 3 or 4 haematological changes,” said Dr Cassella.

The majority of patients in the 12 mg group continued treatment into a long-term open-label extension study. “These promising results support advancement of CTP-543 in the 8 and 12 mg dose into phase 3 trials,” concluded Dr Cassella.

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   1. Cassella J, et al. Late-breaking abstract D3T01.1E, EADV 2019, 9-13 Oct, Madrid, Spain.

 



Posted on 9 December 201917 May 2024