Top-line data from an international Phase 2b clinical trial evaluating ABX464, Abivax’s lead therapeutic candidate for moderate-to-severe ulcerative colitis (UC), are expected later this year, according to the company’s financial report.
In addition, Abivax confirmed its plans to initiate, in the second half of 2020, a similar Phase 2b trial assessing the potent anti-inflammatory therapy’s safety and effectiveness in people with Crohn’s disease (CD).
“Abivax achieved several exciting clinical and regulatory milestones in 2019 and early 2020, making it a very successful year where we delivered on our long-term development strategy,” Hartmut Ehrlich, MD, CEO at Abivax, said in the report.
“With the transformative potential of the efficacy results of ABX464 in ulcerative colitis, our lead product candidate made significant clinical progress and is now in mid-stage clinical testing in Europe and Canada, with patient recruitment allowed in the U.S. after a recently granted IND [investigational new drug application] from the FDA [U.S. Food and Drug Administration],” Ehrlich said.
ABX464, initially developed as a potential treatment for HIV, is an oral small molecule designed to promote the production of miRNA-124, a microRNA molecule which was later found to have strong anti-inflammatory properties.
MicroRNAs, or miRNAs, are small molecules that control genes’ activity by targeting their messenger RNA (mRNA) — the molecule that is used as a template for the production of proteins — and preventing them from making the protein they encode.
Data from a previous Phase 2a clinical trial, called ABX464-101 (NCT03093259) and its open-label, one-year extension study (NCT03368118), known as ABX464-102, showed that daily treatment with 50 mg of ABX464 resulted in “excellent long-term efficacy and continued safety,” the report said.
These studies involved up to 32 adults with moderate-to-severe UC who were intolerant or failed to respond to immunomodulators, TNF inhibitors, Entyvio (vedolizumab), and/or corticosteroids.
The results from the open-label extension study showed that 12 participants (75%) achieved clinical remission and became symptom-free after one year of treatment with ABX464. In addition, ABX464 maintained higher-than-normal levels of miR-124 over the 12-month study period.
Based on these encouraging data, Abivax initiated the Phase 2b ABX464-103 trial (NCT03760003), designed to evaluate the therapy’s safety and effectiveness in up to 232 adults with moderate-to-severe UC.
According to the company, patient enrollment at 126 sites across 15 European countries and in Canada is proceeding according to planned, and U.S. sites are expected to open in the second quarter of 2020. More information about trial’s contacts and enrollment sites can be found here.
The participants will be randomly assigned to receive either one of three daily doses of ABX464 (25 mg, 50 mg, and 100 mg) or a placebo for four months. Top-line data from the study is expected before the end of the year.
After completing the trial, the participants will have the option to enroll in an open-label extension study, called ABX464-104 (NCT04023396), in which all individuals will receive 50 mg of ABX464 daily, for about 11 months.
In the report, the company also highlighted that, to date, some UC patients have been on continuous ABX464 treatment for up to two years. Abivax said ABX464 has shown a “very good clinical safety and tolerability profile along with evidence of superior long-term efficacy,” compared with currently available UC therapies.
Due to ABX464’s positive data so far among those with UC, and the clinical similarities between ulcerative colitis and Crohn’s disease, several key opinion leaders are confident that ABX464 may also be a promising therapeutic option for those with CD, the company said.
Abivax has been encouraged to directly enter a Phase 2b trial evaluating ABX464 in adults with moderate-to-severe CD, and the company is planning to start patient enrollment in the second half of 2020.
ABX464 also is being investigated as a potential treatment for people with rheumatoid arthritis in a Phase 2a trial (NCT03813199). That study is currently recruiting up to 60 participants, ages 18 to 75, with a confirmed and documented diagnosis of adult-onset rheumatoid arthritis.
Regarding the current Covid-19 global situation, Abivax noted that it is “taking necessary measures” to minimize the virus’ impact on ongoing trials and to ensure that patients continue to have access to therapy. The company plans to communicate potential changes as necessary.