Pfizer's JAK3 Inhibitor Ritlecitinib (PF-06651600) Nominated for Breakthrough Therapy Designation in China for Alopecia Areata Treatment

On December 11, Pfizer’s PF-06651600 tablets (ritlecitinib) were proposed by the Center for Drug Evaluation (CDE) to be granted Breakthrough Therapy Designation for the treatment of alopecia areata in patients aged ≥12 years (including alopecia totalis [AT] and alopecia universalis [AU]).

PF-06651600 is an oral targeted Janus kinase 3 (JAK3) inhibitor that achieves selective inhibition of JAK isoforms through covalent interaction with the JAK3-specific residue CYS-909. Compared with first-generation pan-JAK inhibitors, selective JAK inhibitors offer greater advantages in reducing toxicity.

Chemical Structure of PF-06651600

Results from a placebo-controlled Phase II clinical trial in patients with moderate-to-severe alopecia areata showed that after 24 weeks of treatment, the SALT (Severity of Alopecia Tool) score decreased by 32.5 points from baseline in the PF-06651600 group, compared with a decrease of only 1.41 points in the placebo group. (Higher SALT scores [range: 0–100] indicate more severe hair loss.)

In September 2018, PF-06651600 received Breakthrough Therapy Designation from the FDA for the treatment of alopecia areata. Currently, Phase III clinical trials (NCT04006457, NCT03732807) evaluating its efficacy in treating alopecia areata are ongoing. As there are currently no FDA-approved therapies for alopecia areata, the results of the Phase III clinical trials of PF-06651600 are highly anticipated.

According to the CDE Clinical Trial Default Approval Platform, in addition to Pfizer’s PF-06651600, other drugs registered for clinical trials in the treatment of alopecia areata include baricitinib (Eli Lilly), SHR0302 tablets (Jiangsu Hengrui Medicine’s subsidiary, Suzhou Zelgen Biopharmaceuticals), and jakotinib hydrochloride tablets/cream (Suzhou Zelgen Biopharmaceuticals).

Alopecia Areata (AA) is a common inflammatory, non-scarring form of hair loss. It clinically presents as sudden-onset, well-demarcated, circular patches of hair loss on the scalp. Most patients with mild cases experience spontaneous remission, while approximately half suffer from recurrent episodes that may persist for several years or even decades. A minority of patients develop severe disease, with hair loss extending to the entire scalp (alopecia totalis) or even all body hair (alopecia universalis). Clinically, AA is classified into several subtypes: alopecia totalis refers to the complete loss of scalp hair, whereas alopecia universalis denotes the loss of all body hair. The etiology of AA remains incompletely understood; it is currently regarded as a follicle-specific autoimmune disease resulting from the interplay of genetic and environmental factors. AA can occur at any age, is most prevalent among young and middle-aged adults, and shows no significant gender predilection. Epidemiological studies indicate that the prevalence of AA in China is 0.27%.