JAK trial effectively reverses alopecia areata

PARIS―A study presented today at the European Academy of Dermatology and Venereology (EADV) Congress in Paris, showed that two JAK inhibitors met their primary endpoints in a phase 2a study of alopecia areata.

The study, presented by Rodney Sinclair, M.D., of Sinclair Dermatology in Melbourne, Victoria, Australia, focused on the safety and efficacy of  PF-06651600, an oral Janus kinase (JAK) 3 inhibitor; and, PF-06700841, a tyrosine kinase (TYK) 2/JAK1 inhibitor.

Both JAK inhibitors met week 24 primary endpoints by improving hair regrowth scoring 33.6 of 100 points on the Severity of Alopecia Tool (SALT) scale and 49.5 of 100 points for JAK3 and TYK2/JAK1 respectively.

The management of alopecia areata is complex. While spontaneous and treatment-induced recovery occurs in up to 50 percent of cases, this still leaves around 73 million people worldwide who suffer from chronic alopecia areata, or up to 25 percent whom have total hair loss. “Given these figures, there’s an unmet need for a reliable and effective therapy in moderate-to-severe alopecia areata,” Dr. Sinclair said.

Alopecia areata is driven by cytotoxic T lymphocytes and reversed by JAK inhibition. An increasing number of case reports have demonstrated that oral JAK inhibitors are an effective treatment for chronic alopecia areata. However, few randomized controlled trials have investigated the efficacy and safety of JAK inhibitors.

This trial investigated hair regrowth and adverse events in subjects with alopecia areata treated with two JAK inhibitors, PF-06651600 (a potent JAK3 inhibitor) and PF-06700841 (an inhibitor of JAK1 and tyrosine kinase 2). The study recruited an initial 145 adults with moderate-to-severe alopecia areata, which was defined as hair loss affecting more than 50 percent of the scalp that had persisted for more than six months. The trial included a handful of patients with areata totalis and areata universalis.

Subjects were randomly allocated to a PF-06651600 group (n = 48), PF-06700841 group (n = 47), or control group (n = 49). The PF-06651600 group received 200 mg/day during the induction period and 50 mg/day in the maintenance phase. The PF-06700841 group received 60 mg/day during the induction period and 30 mg/day during the maintenance phase. The control group received a placebo.

The mean change of the Severity of Alopecia Tool (SALT) score from baseline revealed significant improvements for both the PF-06651600 and PF-06700841 groups at every measured time point (every four weeks), reaching significance levels of p < 0.001. The control group experienced no improvements in hair regrowth.

At week 24 (vs. baseline), SALT-30 was achieved in 48% of the PF-06651600 group and in 36% of the PF-06700841 group. “A number of subjects in the two treatment groups also achieved SALT-50 to SALT-75, and a significant proportion achieved SALT 90-100,” Dr. Sinclair reported. The patients with areata totalis and areata universalis that received treatment also showed significant improvements in SALT scores and in eyebrow and eyelash scores.

Rhabdomylosis was observed in two cases in the PF-06700841 group, and this was resolved after discontinuation. No other major adverse events were recorded.

“These JAK inhibitors are well-tolerated in patients, including those with areata universalis and areata totalis. Both treatments achieved the primary and secondary endpoints, and safety and tolerability, and I think that our patients with alopecia areata now have reason to be optimistic,” he said.

DISCLOSURES

The featured study was funded by Pfizer.

REFERENCE

Sinclair, R. (2018). A Phase 2a Randomized, Placebo-controlled Study to Evaluate Efficacy and Safety of Janus Kinase Inhibitors PF-06651600 and PF-06700841 in Alopecia Areata: 24-Week Results, The 27th European Academy of Dermatology and Venereology Congress, Paris, France, 15th September, 08:00 AM.