On September 20, the French National Regulatory authority (ANSM) gave Abivax the approval to start its new proof–of-concept Phase IIa study, named ABX464-101, of its drug ABX464. ABX464 is a compound that causes upregulation of interleukin 22 (IL-22), a cytokine that is known to suppress the inflammatory processes. ABX464 also reduces both macrophage recruitment and other inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα), in the large intestine. The innovative French biotechnology company has plans to initiate the study in Q4 of 2017 in adult patients with moderate to severe active ulcerative colitis (UC).
UC is a chronic inflammatory disease of the colon, or large intestine, that usually initially manifests in the terminal part of the colon, the rectum, and extends either to the left part of the colon or to the entire colon as the disease progresses. In 2015, according to GlobalData, there were over 601,000 diagnosed prevalent cases of moderate to severe UC globally across all ages. For patients who are diagnosed with moderate to severe UC, physicians are likely to prescribe corticosteroids to induce remission, in combination with a thiopurine immunomodulator. If the conventional therapies fail to have an effect on the patient, physicians prescribe biologics such as Johnson & Johnson’s Remicade (infliximab), AbbVie’s Humira (adalimumab), Johnson & Johnson’s Simponi (golimumab), or Takeda’s Entyvio (vedolizumab).
Although current medications can help to both induce and maintain remission, efficacy and safety concerns have been identified as an unmet need in the UC space. Regarding the use of corticosteroids as a maintenance therapy, safety concerns remain, stemming mostly from side effects such as hyperglycemia, hypertension, and growth failure. There are also many adverse reactions associated with thiopurine immunomodulators, such as myelosuppression, hepatotoxicity, and flu-like illness in children. Furthermore, Remicade, Humira, and Simponi all have a boxed warning for serious infections and malignancy. Entyvio demonstrates a stronger safety profile, but carries an expensive price tag. Furthermore, more drugs are needed in the space that can confidently reduce the risk of cancer in colitis.
After receiving the go-ahead from the ANSM for initiating ABX464-101 in France, Abivax is currently awaiting decisions from the regulatory and ethics committees of Belgium, Germany, Poland, Hungary, Czech Republic and Spain in order to conduct the study in those countries. The proof-of-concept Phase IIa study will evaluate the safety and efficacy of ABX464 in 30 patients who have failed to respond to conventional therapies such as corticosteroids, immunomodulators, anti-TNFα therapy, and anti-integrin therapy. The study period will last for eight weeks and patients will be randomized to receive 50mg of ABX464 orally or placebo. Clinical remission and mucosal healing of UC lesions within patients will be assessed to see the effect of the compound. As such, it will be interesting to see how ABX464 compares to the standard-of-care treatments for UC, as well as how successful it is in addressing the various unmet needs of the patient population.