Oral JAK Inhibitor for Alopecia Areata Advances to Phase 3

Bruce Jancin

January 06, 2021

An investigational oral selective Janus kinase 1 and JAK2 inhibitor maintained strong efficacy and tolerability for treatment of alopecia areata through 1 year of use in an ongoing open-label extension study of a trio of 24-week, phase 2 randomized trials, James V. Cassella, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

"So far, I'd say that the results are very encouraging from this study, as we see good safety and continued stability of the hair regrowth in the open-label extension," said Cassella, chief development officer at Concert Pharmaceuticals of Lexington, Mass.

The study drug, known for now as CTP-543, is a deuterium-modified form of the selective JAK1/2 inhibitor ruxolitinib. CTP-543 was expressly designed for treatment of alopecia areata, a chronic autoimmune disease for which no Food and Drug Administration–approved therapy exists. Cassella characterized alopecia areata as a "devastating and poorly treated" autoimmune disease which affects men, women, and children of all ages and has a lifetime risk of about 2%.

Participants in the open-label extension were typically in their late 30s, with an average disease duration of 3-4 years. Two-thirds were women, and more than three-quarters were White. Their baseline Severity of Alopecia Areata Tool (SALT) score was in the high 80s, indicative of moderate to severe disease.

About 92% of eligible participants from the three phase 2 trials elected to enroll in the long-term extension, a remarkably high participation rate reflective of the major unmet need for effective treatments for this chronic disease.


Of the 152 patients who enrolled in an ongoing open-label extension, which had been going for 108 weeks at the time of the presentation, 130 who completed at least 1 year on CTP-543 formed the focus of Cassella's presentation. The great majority of participants were on 12 mg twice daily. By week 24 in the original phase 2 trials, SALT scores decreased by more than 50%, compared with baseline, with an average score of about 40. This level of efficacy was maintained through the first 6 months of the extension study – meaning a total of at least 1 year on treatment – in roughly two-thirds of participants, while one-third saw further progressive improvement during the first 6 months of the open-label extension, with SALT scores dropping into the 20-30 range.

"You see remarkable stability of hair regrowth beyond 6 months," Cassella commented. Only 2 patients experienced a clear loss of response during the open-label extension.

Safety and Tolerability

About 15% of patients have dropped out of the long-term study, which in only three cases was because of adverse events. Treatment-emergent adverse events, which occurred in 13% of participants, were rated as mild in 76% and moderate in 21%. The most common were nasopharyngitis, acne, and elevated creatine phosphokinase. Two severe adverse events were deemed "possibly related" to treatment. No new types of side effects have emerged during the long-term extension study. Laboratory monitoring of hemoglobin, neutrophils, and platelets has shown stable levels over time.

An audience member asked how quickly hair loss occurs upon stopping therapy.

"Surprisingly, in the few dose interruptions we've had – for changes in hematologic parameters, for example – we have not seen any hair loss in up to a 3-week time period. It's a very interesting question that we will continue to study," Cassella replied. He added: "The general thinking in the community has been, at some point with JAK inhibitors, you will lose your hair if you stop treatment."

Cassella is an employee of Concert Pharmaceuticals, and has received company stock.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.


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