JAK inhibitor promotes hair growth

JAK inhibitor promotes hair growth in both men, women with androgenetic alopecia

Inflammation plays a key role in male and female pattern hair loss, Neal Walker, DO, president and CEO of Aclaris Therapeutics, said in an interview with Healio Dermatology regarding results from a phase 2 open-label clinical trial in subjects with androgenetic alopecia.

“Looking at the aggregate of the data, any way you looked at it was positive. If you look at target area hair count, the physicians’ global assessment or the subjects’ assessment, they all showed nice results,” Walker said.

The premise for this research came from Angela Christiano, PhD, and her lab at Columbia University.

“She discovered that JAK inhibitors seem to work by promoting the entry of the hair follicle back into the growth phase — the anagen phase,” Walker said. “In recent papers, she has published that part of that action is mediated by local inflammation. There are inflammatory cells that promote the hair follicle stem cell via the JAK signaling. It promotes a resting phase, which you might see clinically as hair loss.”

ATI-502 (Aclaris), an investigational topical Janus kinase (JAK) 1/3 inhibitor, was evaluated in adult women and men with androgenetic alopecia (AGA) and applied to the scalp twice daily for 26 weeks.

Twenty-three of 31 subjects completed 6 months of treatment. Twenty subjects, 14 men and 6 women, had evaluable hair counts, and 22 subjects recorded investigator global assessment and subject self-assessment scores.

The mean change from baseline in non-vellus target area hair count (TAHC) at week 26 was the primary endpoint. The TAHC increase was 15.3 hairs/cm2 in female subjects and 5.6 hairs/cm2 in males, according to a press release from Aclaris.

The investigators rated 16 of 22 subjects (73%) as experiencing increased hair growth, and 18 of 22 subjects (82%) rated themselves as experiencing increased hair growth.

“By inhibiting the local inflammation, you remove that [resting phase and hair loss effect], allowing hair follicle stem cell activation, pushing that follicle back into the anagen phase,” Walker said.

The effect in female subjects was particularly strong, according to Walker. A continued linear hair increase was seen up to 6 months, which is not typical in this condition, he said.

Twelve-month results from this trial are expected by the end of the year.

The treatment is nonhormonal, Walker said, and could be used in a variety of options, such as in monotherapy or in combination with existing therapies.

“One thing that surprised me was how robust the female data was,” Walker said. “ Most people who work in hair loss studies look at males first, then go to females. We just decided to do both. I think that was a pleasant surprise.”

As for the next step, Aclaris will initiate a double-blind, randomized controlled phase 2 dose-ranging clinical trial using higher concentrations of ATI-502 in the first half of 2020.

AGA is the most common form of hair loss, which affects approximately 50 million men and 30 million women in the U.S., according to the release.

“We found that inflammation, in fact, does play a key role in male/female pattern hair loss,” Walker said. “When we were in dermatology residency, that wasn’t dogma. There was a fringe number of dermatologists who thought that perhaps there was a role, but I think we’ve definitively shown that inflammation is a part of this process.” – by Abigail Sutton

JAK inhibitor promotes hair growth in both men, women with androgenetic alopecia

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