JAK Kinase Inhibitors Show Promise in Treating Alopecia

UPDATED -- New research suggests selective oral JAK kinase inhibitors may play a role in treating moderate-to-severe alopecia areata (AA).  The findings were presented at the Inflammatory Skin Disease Summit in Vienna, Austria.

In this phase 2a study, 142 adult patients with AA affecting more than 50 percent of their scalp were randomized 1:1:1 to receive PF-06651600, a JAK3 inhibitor (200 mg once daily [QD] for 4 weeks followed by 50 mg QD for 20 weeks), PF-06700841, a JAK1/Tyk2 inhibitor (60 mg QD for 4 weeks, followed by 30 mg QD for 20 weeks), or placebo.

The 24-week treatment with either PF-06651600 or PF-06700841 was efficacious and well tolerated in patients with moderate to severe AA, the study showed. Both JAK inhibitors demonstrated efficacy in achieving the primary endpoint (Severity of Alopecia Tool (SALT) score from baseline) and secondary endpoints (SALT 30, 50, 75). For all efficacy outcomes, PF-06700841 achieved numerically greater effect than PF-06651600 at Week 24. At Week 24, both JAK inhibitors differentiated in percent change in SALT score from baseline (PF- 06651600/JAK3: 33.6 percent, P<0.001; PF-06700841/JAK1/Tyk2: 49.5 percent, P<0.001), and had acceptable safety profiles. The clinical effect of PF-06651600 and PF-06700841 in AA is also supported by the normalization of keratin expression within affected tissues, as clinical improvement was associated with significant increases in several hair keratin-associated genes (i.e KRT40) that were down regulated in baseline pre treatment lesions. Increases in hair keratins were already evident by week 12, with further increases at week 24, according to researchers led by Emma Guttman-Yassky  MD, PhD, the Vice Chair for Research in the Department of Dermatology and the Director of the Center for Excellence in Eczema at Mount Sinai Hospital in New York City.

"This study is very promising [and] the very first randomized study that is placebo controlled," says Dr.Guttman-Yassky. Both drugs achieved all primary and secondary endpoint and are moving forward with larger studies toward approval, she adds. "My lab also did the mechanistic analyses of this study that will enrich the understanding of the pathways that are involved in AA and affected by JAK inhibitors in scalp tissues." 

Calling it a "a very exciting time for alopecia patients," she says that the JAK inhibitors used in the study "hold great promise as we saw patients with no hair all over the body [who] regained all the hair and [this] gives hope to many millions of other sufferers around the globe," she says. "Next research steps is to see what are the factors that determine response and extend studies to children and adolescents that very much need these treatments."