Conference Coverage

Deuterium-altered ruxolitinib may be an effective treatment for alopecia areata



– Yet another inhibitor of the Janus kinase enzyme has debuted with positive phase 2 results for patients with even longstanding alopecia areata.

Courtesy Concert Pharmaceuticals, Inc.

Dr. James V. Cassella

About half of those who took 8 mg of CPT-543, a chemically altered form of ruxolitinib, twice a day for 24 weeks, regrew hair – including eyebrows and eyelashes – by at least 50%. The dose-ranging study also found that a 4 mg twice-daily dose promoted the same growth in 21%, James V. Cassella, PhD, said during a late breaking clinical trials session at the annual meeting of the American Academy of Dermatology.

Adverse events were mild, including headache, reported in 26% of the 8 mg group. However, investigators “are keeping an eye” on infections and blood chemistry, and in light of the confirmed increased risk of herpes zoster and suspected increased risk of thromboembolic events with ??ruxolitinib, said Dr. Cassella, chief development officer of Concert Pharmaceuticals, which is developing the molecule.

Ruxolitinib, an inhibitor of both JAK1 and JAK2, is available under the name Jakafi and is approved for the treatment of myelofibrosis and polycythemia vera. The addition of deuterium slows its metabolism, increasing half-life and bioavailability without affecting receptor selectivity or potency, according to the company.

The company’s 24-week phase 2b study randomized patients with moderate to severe alopecia areata to CPT-543 at 4 mg twice daily (28), 8 mg twice daily (38), or placebo (35). The primary endpoint was the proportion of patients with at least a 50% relative reduction in scalp hair loss as measured by the Severity of Alopecia Tool (SALT) at 24 weeks, from baseline. Secondarily, the trial examined response by alopecia subtype (patchy or complete) and individual SALT changes compared with baseline.

Courtesy Concert Pharmaceuticals, Inc.

Clinical response to CPT-543 in woman with alopecia areata in the study, with regrowth of scalp hair, eyebrows, and eyelashes.

Patients were generally in their mid-30s, and about 75% were female. The mean current alopecia episode was about 5 years. The mean SALT score at baseline was about 89, with 100 being complete hair loss.

By week 24, 47% of those taking 8 mg twice daily and 21% of those taking 4 mg twice daily experienced the primary endpoint of at least 50% SALT reduction from baseline. Almost 9% of those taking placebo also hit the target. These patients all had patchy alopecia and may have been coming out of an alopecia episode during the trial, Dr. Cassella said.

Courtesy Concert Pharmaceuticals, Inc.

Clinical response to CPT-543 in a male patient in the study, with regrowth of scalp hair, eyebrows, and eyelashes.

Week 12 was the inflection point for response division, with both active groups significantly outperforming the placebo group. By week 16, 30% of the 8 mg group and about 15% of the 4 mg group had already hit the primary endpoint. Response in the 4 mg group climbed slowly until the end of the trial, while in the 8 mg group, response ascended more quickly. Response was still trending upward when the study stopped.

“We think we have not hit the ceiling effect with this drug,” Dr. Cassella said. “There is some evidence that response would continue to increase after 24 weeks.”

Patchy alopecia and alopecia universalis appeared to respond best to treatment in both dosage groups. There was no response in either group for patients with alopecia ophiasis or totalis.

Headache was the most common adverse event, and appeared to be dose-dependent, occurring in 11% of placebo patients, 17% of the 4 mg group, and 26% of the 8 mg group. Six patients developed increased blood creatinine phosphokinase levels (one in the placebo group, three in the 4 mg group, and two in the 8 mg group). There were no thromboembolic events. Three patients in the placebo group and two in the 8 mg group discontinued the medication due to unspecified adverse events.

In early March, the company announced an open-label dose-finding study, which will randomize 60 patients with moderate-to-severe alopecia areata to either 8 mg twice daily or 16 mg once daily over a 24-week treatment period. Concert intends to conduct a food-effect trial to assess the relative bioavailability of oral doses of CTP-543 under fasted and fed conditions in 14 healthy volunteers in the first half of 2019.

SOURCE: Casella J. AAD 2019; S034, Abstract 11291.

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