* PF-06651600 (
JAK3)--In January 2019, Pfizer announced the initiation of a pivotal Phase 2b/3 clinical trial for its oral
JAK3 inhibitor, PF-06651600, for the treatment of patients with moderate to severe alopecia areata, a chronic autoimmune skin disease that causes hair loss on the scalp, face, or body, and currently has no approved therapies.
The analysis of the whole transcriptome data revealed different expression levels of several genes, such as JAK1, JAK2,
JAK3, RAF, IL6R, NCAM (CD56), WHSC1, MCL1, BCL2, and IGF1, which showed myeloma pathogenesis as reported previously.
The phase 2 multicenter, placebo-controlled, double-blind study randomized 142 patients with chronic alopecia of at least 6 months duration and 50% or greater hair loss at baseline to an oral Janus kinase 3 (
JAK3) inhibitor known for now as PF-06651600, an oral tyrosine kinase 2 (TYK2)/JAK1 inhibitor known as PF-06700841, or placebo for 24 weeks.
Next-generation sequencing (NGS) was available in seven patients using a custom-designed 49 genes' panel (Ion S5™ System, Thermo Fisher, San Diego, CA, USA), including the entire coding region of ASXL1, ASXL2, BCOR, BCORL1, BIRC3, BRAF, CALR, CBL, CDKN2A, CSF3R, CSMD1, DNMT3A, ETNK1, ETV6, EZH2, FBXW7, FLT3, GATA2, IDH1, IDH2, IL7R, JAK1, JAK2,
JAK3, KIT, KRAS, MPL, MYD88, NOTCH1, NRAS, PAX5, PDGFRA, PDGFRB, PHF6, PIGA, PTEN, PTPN11, RUNX1, SETBP1, SETD2, SF3B1, SH2B3, SRSF2, STAG2, TET2, TP53, U2AF1, WT1 , and ZRSR2 , with a median depth of x2000.
Pfizer said that based on the "totality of the data and the emerging clinical profiles," the investigational
JAK3 inhibitor, which was recently granted Breakthrough Therapy designation from FDA for alopecia areata, is advancing to the next phase of development for moderate to severe alopecia areata and will continue to be evaluated for rheumatoid arthritis, Crohn's disease and ulcerative colitis.
