AbbVie Submits IND Application in China for BTK Inhibitor ABBV-105 Capsule

Compiled by: Linan

On September 27, the CDE website showed that AbbVie's BTK inhibitor ABBV-105 capsules have been submitted for clinical trial application in China, marking the first time this drug has been applied for clinical trials domestically.

Bruton tyrosine kinase (BTK) belongs to the Tec family of non-receptor tyrosine kinases and is a key kinase in the B cell receptor (BCR) signaling pathway. Overexpression of BTK leads to aberrant activation of the BCR pathway, affecting B-cell proliferation, differentiation, and apoptosis, thereby contributing to the development of various malignant lymphomas, primarily B-cell lymphomas within the category of non-Hodgkin lymphoma. Furthermore, BTK overexpression-induced aberrant activation of the BCR signaling pathway can cause B-cell dysfunction and alter immune tolerance, leading to the transformation into autoreactive B cells that secrete large amounts of autoantibodies, thus triggering autoimmune diseases. Based on these mechanisms, research on the application of BTK inhibitors in autoimmune diseases, including rheumatoid arthritis, has been increasingly conducted in recent years.

ABBV-105 is an irreversible BTK inhibitor with an IC50 of 0.18 μM. It irreversibly inhibits BTK, demonstrates superior kinome selectivity, and is effective in B cell receptor-, Fc receptor-, and TLR-9-dependent cellular assays; it inhibits antibody responses to thymus-independent and thymus-dependent antigens, paw swelling, and bone destruction in rat collagen-induced arthritis (CIA), and reduces disease severity in the IFNα-accelerated lupus nephritis model.

Notably, most research on BTK inhibitors for autoimmune diseases is still in Phase I and II clinical trials. In fact, whether for lymphoma or autoimmune diseases, there are currently no BTK inhibitors in Phase III clinical trials.

AbbVie’s Product Advances in the Rheumatoid Arthritis (RA) Field

It is reported that AbbVie’s ABBV-105 has currently entered Phase II clinical trials in the United States, and its combination therapy with the JAK1 inhibitor upadacitinib has also advanced to Phase II clinical trials.

Reference Article:

1. PharmDj “BTK Inhibitors for the Treatment of Autoimmune Diseases” (2019-01-18)

2. PharmCube: “The $30 Billion Rheumatoid Arthritis Drug Market: Who Will Dominate?” (2019-04-14)