Abivax (Euronext Paris: FR0012333284 – ABVX), a clinical-stage biotechnology company harnessing the immune system to develop novel treatments for inflammatory diseases, viral diseases and cancer, announced two-year Phase 2a maintenance data of ABX464 in ulcerative colitis (UC), showing that 69% of the patients were in clinical remission and 94% benefited from a clinical response. The patients suffering from moderate-to-severe UC were all intolerant and/or refractory to at least one existing treatment prior to entering the ABX464 study. These data confirm good safety and efficacy results of ABX464 during the second year of treatment, which were already observed during the induction and first year of the maintenance study.
Ulcerative Colitis (UC)
The cause of UC is unknown but theories center on immune system dysfunction, genetics, changes in the normal gut bacteria and environment factors. Rates are generally higher in the developed world, indicating possible culprits such as the “Western” diet and lifestyle.
This long-term condition results in inflammation and ulcers of the colon and rectum. Primary symptoms often include abdominal pain and diarrhea mixed with blood. Other conditions such as weight loss, fever, and anemia can occur. Symptoms can occur intermittently and at times the patient may experience no material symptoms between flare ups.
Incidents of UC continue to rise, totaling up to 2-299 per 100,000. By 2015, there were 47,400 deaths combining UC and Crohn’s disease. About 11.2 million people are affected by UC plus Crohn’s disease combined by 2015.
The condition is treated by one of a number of medications, from 5-ASA drugs to corticosteroids; however, risks outweigh benefits for any long-term use. Immunosuppressive drugs (azathioprine or biologics such as infliximab and adalimumab) are prescribed if patients cannot achieve remission with 5-ASA and corticosteroids. Often, infliximab or vedolizumab can be recommended with moderate or severe conditions. But they include significant A specific formulation of budesonide was approved by the U.S. Food and Drug Administration (FDA) for treating active UC back in 2013. By 2018, tofacitinib was approved for treatment of moderately to severely active UC in the United States, actually the first oral medication indicated for long term use. Some off label drugs such as cyclosporin and tacrolimus have evidenced some benefits.
This study (NCT04023396) is currently ongoing in 15 European countries, Canada, and the US; and enrollment is on track with 69% (159/232) patients randomized to date in the induction study. Patient recruitment is expected to be completed by the end of this year with first top-level results to be communicated in Q2/2021. Out of 85 patients who completed the induction phase, only one patient did not roll over into the maintenance study, while the remaining 84 patients did. All patients in the maintenance study are receiving daily doses of 50mg oral ABX464, which shows a good safety profile consistent with previous studies. The clinical program in UC is Abivax’s top priority and all necessary steps to further progress into Phase 3 studies are being prepared.
Out of 32 patients included in the active or placebo arm of the initial induction phase, 22 were enrolled in the 50mg once-daily open label ABX464 Phase 2a maintenance study. 19/22 patients stayed on treatment for 52 weeks and 16/19 patients completed the second year of ABX464 maintenance treatment. Readings for all endoscopies were performed centrally by independent reviewers. The data showed that 11/16 (69%) patients were in clinical remission and 15/16 (94%) benefited from a clinical response. 7/16 (44%) had endoscopic remission consisting of complete disappearance of colon/rectum lesions (endoscopic Mayo score=0). Median fecal calprotectin, the key biological marker of UC disease activity, which was normalized during the first year of treatment, remained at 31.6 µg/g (normal levels are below 50 µg/g).
ABX464 was safe and well tolerated and there were no serious adverse drug reactions reported. No patients were prematurely discontinued due to adverse event during this second year of ABX464 treatment.
Principal Investigator POV
Principal Investigator Professor Séverine Vermeire, MD, PhD, Head of the IBD Center at the University Hospitals Leuven, Belgium, reported, “The safety and durability of clinical efficacy after two years of continued treatment of UC patients, intolerant or refractory to existing treatments, are very promising. Especially as the central and independent endoscopy readings after two years confirm the good one-year maintenance results, where endoscopies were read locally. We are very motivated to continue enrolling patients in the ongoing ABX464 Phase 2b induction and maintenance study and hope to be able to confirm the findings from the Phase 2a study.”
Meanwhile Professor William Sandborn, MD, Director of the Inflammatory Bowel Disease (IBD) Center at University of San Diego Health, and Chief, Division of Gastroenterology at UC San Diego School of Medicine, commented: “The two-year Phase 2a maintenance results confirm the potential of ABX464 to become a treatment option for UC patients who do not respond or stop responding to currently available treatments after a certain period of time, including biologics. This debilitating disease greatly affects patients’ quality of life and requires expensive and cumbersome therapies. The innovative mechanism of action of ABX464 and data from this trial represent a promising new potential approach to the treatment of ulcerative colitis that could provide these patients with an easily administered, once-daily oral, long-term effective therapeutic option.
Update on Other Ongoing and Planned Clinical Trials With ABX464:
Enrollment in the Phase 2a trials in rheumatoid arthritis is progressing well, with anticipated completion of recruitment by year-end. The Phase 2b/3 clinical trial in COVID-19 patients has been approved in all participating European countries and Brazil, where recruitment is ongoing and expected to be completed in Q4/2020, subject to the evolution of the pandemic. Following the recommendations of leading KOLs, Abivax is planning to go straight into a pivotal Phase 2b/3 trial for Crohn’s disease, which is expected to start recruiting beginning of 2021.
Founded in 2013, Abivax has raised 32 million Euros. The clinical stage biopharmaceutical venture leverages its multiple drug development platforms to treat patients with viral infections, inflammatory diseases, and cancer. The company’s intellectual property is based on innovative research driven by the idea of stimulating the body’s natural immune system mechanisms to cure diseases with three programs in clinical trials and four products in Research and Preclinical development. The company is currently targeting two main indications for its ABX464 compound: fighting inflammatory diseases and specifically IBD (inflammatory bowel disease). The company also is developing what it positions as a functional cure for HIV. See their pipeline.