AbbVie's JAK1 and BTK Inhibitor Combination Therapy ABBV-599 Receives Clinical Trial Approval in China for Systemic Lupus Erythematosus

Latest Public Notice from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration: AbbVie’s Upadacitinib Tablets and Elsubrutinib (ABBV-105) Capsules Have Received Implicit Approval for Three Clinical Trials, with Plans to Develop the Combination Therapy for Moderate-to-Severe Active Systemic Lupus Erythematosus (SLE).

Upadacitinib is a JAK1 inhibitor that was approved in the United States in August 2019 for the treatment of patients with active rheumatoid arthritis and was once rated by EvaluatePharma as one of the most valuable drugs under development. Elsubrutinib is an investigational BTK inhibitor.

Source: CDE Official Website

JAK1 is a member of the JAK protein kinase family. Given the critical role of JAK-mediated cytokine signaling pathways in immune-mediated and neoplastic diseases, the JAK kinase family has emerged as an important therapeutic target for these conditions. BTK is a key component of the B-cell antigen receptor (BCR) signaling pathway. Studies have shown that overexpression of BTK leads to B-cell dysfunction, alterations in immune tolerance, and transformation into autoreactive B cells that secrete large amounts of autoantibodies, thereby inducing autoimmune diseases. Consequently, BTK inhibitors hold potential for the treatment of autoimmune diseases.

Based on these findings, scientists are also exploring the efficacy of combination therapy with innovative drugs targeting these two pathways for autoimmune diseases. The drug recently approved by AbbVie for clinical trials is a combination therapy of a JAK inhibitor and a BTK inhibitor.

Upadacitinib is a once-daily, oral, small-molecule selective JAK1 inhibitor developed by AbbVie. In August 2019, the drug was approved by the U.S. FDA for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). Currently, AbbVie is developing upadacitinib for the treatment of various autoimmune diseases, including Crohn’s disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis, and systemic lupus erythematosus.

Elsubrutinib is an irreversible BTK inhibitor developed by AbbVie, and it has not yet been approved for marketing in any region.

Public information indicates that the combination therapy of “upadacitinib + elsubrutinib” is designated under AbbVie’s development code ABBV-599. According to ClinicalTrials.gov, AbbVie is evaluating the therapeutic efficacy of ABBV-599 in multiple diseases, including rheumatoid arthritis and systemic lupus erythematosus. Among these, two are Phase 2 clinical trials targeting systemic lupus erythematosus:

A Study to Evaluate the Safety and Efficacy of Upadacitinib + Elsubrutinib (ABBV-599) as Monotherapy or Combination Therapy in Patients with Moderate to Severe Active Systemic Lupus Erythematosus;

Another phase 2 extension study aimed to evaluate the efficacy of upadacitinib + elsubrutinib (ABBV-599) administered either individually or in combination, among patients with moderate-to-severe active systemic lupus erythematosus who had completed the phase 2 randomized controlled trial (RCT) M19-130.

The Chinese Drug Clinical Trial Registration and Information Publicity Platform shows that AbbVie had previously registered a Phase 2 clinical study aimed at evaluating the safety and efficacy of upadacitinib + elsubrutinib, either as monotherapy or in combination (ABBV-599), in subjects with moderate to severe active systemic lupus erythematosus.

Lupus is a chronic autoimmune disease in which the patient’s immune system attacks their own tissues, leading to a variety of symptoms. Over the past 60 years, only one new biologic agent has been approved for the treatment of systemic lupus erythematosus (SLE). SLE can manifest in several ways, including rash, arthritis, anemia, thrombocytopenia, serositis, nephritis, seizures, or psychosis. Joint pain or swelling is one of the most common symptoms affecting the quality of life in patients with SLE.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Nov 26, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=25

[2] AbbVie Receives FDA Approval of RINVOQ™ (upadacitinib), an Oral JAK Inhibitor For The Treatment of Moderate to Severe Rheumatoid Arthritis. Retrieved August 16, 2019, from https://www.prnewswire.com/news-releases/abbvie-receives-fda-approval-of-rinvoq-upadacitinib-an-oral-jak-inhibitor-for-the-treatment-of-moderate-to-severe-rheumatoid-arthritis-300903053.html

Source: Medicine Review

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