Ritlecitinib (Litfulo): A Comprehensive Clinical and Pharmacological Monograph

Executive Summary

Ritlecitinib, marketed under the brand name Litfulo, represents a significant therapeutic advancement in the management of severe alopecia areata (AA). It is a first-in-class, orally administered small molecule that functions as a dual irreversible inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) family of kinases. This novel mechanism of action selectively targets key immunological pathways implicated in the pathogenesis of AA.

Developed by Pfizer, ritlecitinib has achieved landmark regulatory approvals from major global health authorities, including the U.S. Food and Drug Administration (FDA) in June 2023 and the European Medicines Agency (EMA) in September 2023.[1] A key differentiator in its approval is its indication for use not only in adults but also in adolescents aged 12 years and older with severe AA, making it the first therapy sanctioned for this younger patient population, which previously had no approved systemic options.[3]

The clinical efficacy of ritlecitinib was robustly established in the pivotal ALLEGRO Phase 2b/3 and long-term extension studies. These trials demonstrated statistically significant and clinically meaningful scalp hair regrowth, as measured by the Severity of Alopecia Tool (SALT), with a notable proportion of patients achieving SALT scores of ≤20 (80% or more scalp coverage). The response has been shown to be durable and to deepen over time with continued treatment.[5] Efficacy was also observed in eyebrow and eyelash regrowth.