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ABX464 begins rheumatoid arthritis trial
PARIS—Abivax SA, a clinical-stage biotechnology company harnessing the immune system to develop novel treatments for inflammatory diseases, viral diseases and cancer, announced today that the first patient was dosed in study ABX464-301, a Phase 2a clinical trial of ABX464 to treat patients with moderate to severe active rheumatoid arthritis (RA). The trial has been fully approved in four countries — France, Poland, the Czech Republic and Hungary.
ABX464 is an oral once-daily drug candidate with a novel mechanism of action that binds to the cap binding complex (CBC), thereby reinforcing the biological functions of this complex in cellular RNA biogenesis. ABX464 enhances the selective splicing of a single long non-coding RNA to generate the anti-inflammatory microRNA miR-124, which downregulates pro-inflammatory cytokines and chemokines like TNF-a, Il-6 and MCP-1, putting a brake on inflammation and suggesting broad potential as a novel anti-inflammatory therapeutic agent. ABX464 has already demonstrated positive results in ulcerative colitis (UC), another severe chronic inflammatory disease with closely related biological etiology.
“We are pleased to initiate the first clinical trial of ABX464 in patients with moderate to severe active rheumatoid arthritis, the largest market opportunity in inflammatory disease,” said Professor Hartmut J. Ehrlich, M.D., chief executive officer of Abivax. “The robust, sustained Phase 2a clinical ulcerative colitis efficacy, demonstrating ABX464’s rapid, potent anti-inflammatory effects, together with ABX464’s broad efficacy in preclinical inflammatory disease models, suggest that ABX464 may have important potential as a novel, highly differentiated anti-inflammatory therapeutic agent. ABX464’s novel mechanism of action, published in Nature Scientific Reports in January 2019, illustrates how this orally available molecule is differentiated and offers a potentially complementary mechanism of action compared to marketed anti-inflammatory agents.”
“Thanks to the recent EUR12 million investment by Sofinnova Partners, we are moving, as planned, to accelerate the development of this first-in-class therapeutic candidate to treat rheumatoid arthritis. Also, the Phase 2b trial of ABX464 to treat ulcerative colitis is progressing well, with the ‘first patient dosed’ expected for the next two weeks. Furthermore, we look forward to initiating, around the end of this or early next year, a Phase 2a trial of ABX464 to treat Crohn’s disease,” Ehrlich continued.
ABX464-301 is a Phase 2a study designed to evaluate the safety, tolerability and preliminary efficacy of two oral dose-levels of ABX464 administered daily, in combination with methotrexate (MTX), in patients with moderate to severe active RA who had an inadequate response to MTX and/or to one or more anti-tumor necrosis factor alpha (TNFα) biological therapeutics. It is a randomized, double-blind, placebo-controlled multicenter study in sixty patients with moderate to severe active RA, who will receive 50 mg ABX464, 100 mg ABX464, or placebo during the twelve-week treatment phase.
The primary endpoint of the study will be safety and tolerability. Secondary endpoints will include measures of efficacy, such as change from baseline in the individual components of the American College of Rheumatology (ACR) score, proportion of patients achieving ACR20 response, and change from baseline in Disease Activity Scores (DAS) in 28 joints.
“Rheumatoid arthritis is an irreversible, debilitating, and systemic autoimmune disease that often requires aggressive treatment to control. This disease represents a major burden for the millions of affected patients, their families and for healthcare systems worldwide. The standard of treatment has substantially evolved during the past two decades, now including conventional disease-modifying antirheumatic drugs (DMARDs) used as first line, like methotrexate, leflunomide, hydroxychloroquine, sulfasalazine but also biologic DMARDs (anti-TNF) as well as targeted DMARDs (JAK-inhibitors),” added Dr. Jean-Marc Steens, chief medical officer of Abivax. “However, too many patients do not respond or loose responsiveness to these drugs, and new molecules with a different mechanism of action, like ABX464, are needed.”
Topline data from the ABX464-301 trial are expected in about a year, during the summer of 2020.