Investigational JAK inhibitor found safe, effective in moderate to severe alopecia areata in phase 3 study

Alopecia areata is an autoimmune disorder that results in patchy or complete scalp hair loss. CTP-543 is an investigational oral selective inhibitor of Janus kinase 1 (JAK1) and JAK2. In adults with moderate to severe alopecia areata, positive topline results were announced from a Phase 3 clinical trial, THRIVE-AA1, evaluating the efficacy and safety of CTP-543.

The primary efficacy endpoint for THRIVE-AA1 was the percentage of patients achieving an absolute Severity of Alopecia Tool (SALT) score of 20 or less at Week 24 of treatment, which was met with statistical significance in both the 8 mg twice-daily and 12 mg twice-daily dose groups relative to placebo. Treatment with CTP-543 was generally well tolerated.

The key secondary endpoints were the percentage of responders on a Hair Satisfaction Patient Reported Outcome (PRO) scale at Week 24 and the percentage of patients achieving absolute SALT scores of 20 or less at each of Weeks 20, 16, 12 and 8. All key secondary endpoints were met with statistical significance in both dose groups.

"Today marks an important milestone in advancing new treatments for alopecia areata, and I'm so happy to see such positive results from the first Phase 3 trial with CTP-543," said Brett King, M.D., Department of Dermatology, Yale University School of Medicine and clinical investigator of THRIVE-AA1. "There is a great need for treatments for this challenging disease, and the results from the THRIVE-AA1 trial suggest that CTP-543 may potentially provide an important therapy for treating alopecia areata."

"With these compelling Phase 3 data, we believe that CTP-543 has the potential to be a best-in-class treatment for patients with alopecia areata, a disease that has long been ignored. We are extremely grateful to the patients and teams of clinical research professionals who participate in our trials," said James V. Cassella, Ph.D., Chief Development Officer of Concert Pharmaceuticals.

"We're working to change the treatment landscape and hope that CTP-543 will be one of the first FDA-approved treatment options for this serious disease."

Patients enrolled in THRIVE-AA1 were required to have at least 50 percent scalp hair loss due to alopecia areata, as measured by SALT. A SALT score of 100 represents total scalp hair loss whereas a score of 0 represents no scalp hair loss. The average baseline SALT score across all patients was approximately 85.9 (corresponding to less than 15% average scalp hair coverage).

A statistically significant proportion of patients treated with either 8 mg twice-daily or 12 mg twice-daily of CTP-543 experienced greater scalp regrowth compared to placebo. The proportion of patients achieving a SALT score of 20 or less (meaning that 80 percent or more scalp hair coverage was achieved) was 41.5 percent in the 12 mg twice-daily dose group and 29.6 percent in the 8 mg twice-daily dose group, compared to 0.8 percent of patients in the placebo group, at the 24-week endpoint. The treatment difference for both dose groups of CTP-543 relative to placebo was statistically significant (p<0.0001).

The safety profile seen with CTP-543 in THRIVE-AA1 was consistent with previous studies. The most common (≥5%) side effects in any dose group were headache, acne, upper respiratory infection, increased creatine kinase levels, COVID-19 infection and nasopharyngitis. Upper respiratory infections were greater in the placebo group than in either of the CTP-543 dose groups. No pulmonary embolisms or deep vein thromboses were observed in the trial.

One patient treated with the 8 mg twice-daily dose and one patient treated with the 12 mg twice-daily dose developed herpes zoster (shingles). Serious adverse events were reported in nine patients, with only one patient (in the 8 mg twice-daily dose group) having events (2) that were assessed as possibly related to treatment. Four patients who reported serious adverse events were in the placebo group.

Concert expects to submit the full results from this study for future scientific publication and presentation. These data, along with data from THRIVE-AA2, a second Phase 3 clinical trial, are intended to form the basis of a New Drug Application (NDA) planned to be submitted to the U.S. Food and Drug Administration (FDA) in the first half of 2023, assuming positive results from THRIVE-AA2. Topline data from THRIVE-AA2 are expected in the third quarter of 2022.