AbbVie Upatinib Approved in my country to Inventory 8 Iteratively Marketed JAK Inhibitors Worldwide

Text by Bu Yuan

On February 24, the official website of China's National Medical Products Administration (NMPA) showed that AbbVie's JAK inhibitor upadatinib sustained-release tablets was officially approved.

Previously, upatinib has been approved by the US FDA for rheumatoid arthritis (RA), psoriatic arthritis (PsA), and atopic dermatitis (AD)-related indications

JAK inhibitors are currently one of the most concerned medical research directions in the world.

However, despite the many achievements, the road ahead for JAK inhibitors is not so easy

Previously, because the FDA has issued risk warnings to JAK inhibitors and has repeatedly delayed the review of JAK inhibitor drugs, the safety challenges of JAK inhibitors have always attracted the attention of the industry

01

JAK inhibitors

The English name of JAK kinase is Janus Kinase, abbreviated as JAK.

The JAK-STAT pathway is one of the few immunomodulatory pathways that have been proven so far, so JAK inhibitors can play a role in the field of autoimmune diseases

Currently, JAK has discovered four family members:

JAK1: mainly related to acute lymphoblastic leukemia, acute myeloid leukemia, solid organ malignancies; JAK2: mainly related to polycythemia vera, myelofibrosis, essential thrombocythemia and other diseases; JAK3: mainly related to acute megaloblastic Cell leukemia, T cell leukemia and lymphoma and other diseases; TYK2: mainly related to skin lymphoproliferative diseases and T cell leukemia

The main JAK inhibitors that have been approved in the world are (based on the time of first listing):

In 2011, the oral, ATP-competitive, and reversible JAK1/2 inhibitor ruxolitinib (Jakafi) studied by Incyte/Novartis was approved by the US FDA for the treatment of myelofibrosis (MF)

.

Among these approved JAK inhibitors, they are divided into—

First-generation non-selective JAK inhibitors: ruxolitinib, tofacitinib, baricitinib, peficitinib, delgocitinib Second-generation selective JAK inhibitors: AbbVie’s upatinib (Rinvoq), Sanofi/Celgene’s fedratinib (Inrebic), Pfizer’s abrutinib (Cibinqo)

In general, the first-generation non-selective JAK inhibitors all contain similar structures of adenine in ADP, so they generally have the problem of low selectivity.

Second-generation JAK inhibitors can selectively inhibit JAK family members, so they can inhibit specific disease-related signaling pathways while maintaining the function of other cytokines unaffected, which is based on research and development

02

Approved JAK inhibitors in my country and their research status

With the approval of AbbVie Upatinib, 4 JAK inhibitors have been approved in China, and the remaining 3 are: Novartis' ruxolitinib, Eli Lilly's baricitinib, and Pfizer's tofacitinib Cloth, the indications mainly cover rheumatoid arthritis, myelofibrosis, atopic dermatitis

In addition, the pharmaceutical companies that are currently deploying JAK inhibitors in my country and with rapid clinical progress mainly include:

Hengrui Medicine's JAK1 inhibitor - SHR0302, for rheumatoid arthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis

.

It can be seen that JAK inhibitors are being developed in full swing in China and around the world, but their potential dangers are gradually being exposed, especially in the past two years, the FDA has warned that JAK inhibitors cause serious heart-related events, cancer, thrombosis and the risk of death.

Reference: Pharmaceutical Guanlan "JAK Inhibitor in Iteration! A target favored by major companies such as Pfizer, Eli Lilly and Novartis”