Eli Lilly and Company and Incyte jointly announced on Mar. 3, 2021 that baricitinib, an oral JAK inhibitor, met its primary endpoint in Phase 3 clinical trial for the treatment of adult patients with severe alopecia areata (AA). After 36 weeks of treatment, the drug significantly improved hair regrowth compared to the placebo group.
AA is an autoimmune disease that mainly causes patchy hair loss on the scalp, face and other areas of the body. The average age of onset of AA is between 25 and 35 years old, however, it can also affect children and teenagers and occur in both sexes and all races. More than half of AA patients experience health-related deterioration in the quality of life, and AA can also lead to serious psychological disorders such as depression and anxiety.
Baricitinib is an oral JAK3 inhibitor. JAK belongs to a family of cytoplasmic tyrosine kinases with four subtypes: JAK1, JAK2, JAK3, and TYK2, and subtypes are overlapping in the bound objects. JAK kinases are considered to play an important role in inflammation because they are involved in the signaling of more than 50 cytokines and growth factors, many of which are involved in driving immune-mediated reactions. The inhibitors of this family of kinases have shown efficacy in the treatment of certain inflammatory and autoimmune diseases.
Baricitinib has been approved in more than 70 countries as a treatment for moderate to severe active rheumatoid arthritis, with the trade name being Olumiant, and it has received Breakthrough Therapy designation from the FDA for the treatment of AA.
This BRAVE-AA2 study included 546 patients who had ≥50% scalp hair loss (SALT score ≥ 50) and severe AA lasting at least six months but no more than eight years. The study included a diverse patient population from China, South Korea, Japan, Brazil, Australia, Argentina, the U.S., etc. In Phase 2, according to the 36-week treatment results, no new severe adverse events were discovered in the baricitinib group compared to the placebo group, and treatment-related adverse events were mild to moderate, mainly including upper respiratory tract infections, nasopharyngitis, and acne. Phase 3 mainly assessed the differences in efficacy and safety between 2-mg and 4-mg baricitinib and the placebo.
The trial results showed that both doses of baricitinib met the primary efficacy endpoint at week 36, with safety outcomes consistent with its established safety profile in patients with rheumatoid arthritis and atopic dermatitis. Detailed results will be presented at an upcoming medical conference and published in a peer-reviewed journal later this year.
Besides baricitinib, there has been a boom in the development of blockbuster JAK inhibitors in recent years, which are effective in many diseases.
Market layout
1. Pfizer: PF-06651600
PF-06651600 is a JAK3 inhibitor that has received Breakthrough Therapy designation from the FDA for the treatment of AA. Based on a Phase 2a, randomized, double-blind, multicenter trial, PF-06651600 met the primary efficacy endpoint of promoting hair regrowth in the treatment of moderate to severe AA: relative to baseline at week 24, the SALT (Severity of Alopecia Tool) score improved to 33.6 points and 49.5 points (out of a maximum of 100), respectively.
Pfizer is currently conducting two Phase 2b/3 international multicenter clinical trials in China in AA subjects. Globally, the product will also continue to be tested for the treatment of rheumatoid arthritis, Crohn’s disease and ulcerative colitis.
2. Innovent/Incyte: itacitinib
Itacitinib is a novel, potent, small-molecule selective inhibitor of the JAK1 signaling pathway. Innovent has entered into an exclusive license agreement with Incyte to advance the clinical development and commercialization of three new oncology drugs, including itacitinib, as monotherapies or combination therapies in Greater China. These two companies received a clinical trial implied permission in Nov. 2019 for itacitinib in China, with the proposed indication of graft-versus-host disease.
3. Hengrui Medicine/Reistone Biopharma: SHR0302
SHR0302 is a highly selective small-molecule JAK1 kinase inhibitor. Its selectivity for JAK1 is more than 10 times that for JAK2, 77 times th...
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