Candidate: ABX464
Category: RNA
Type: Oral, once-daily upregulator of miR-124, a physiological microRNA that down-regulates cytokine signaling and inflammation, promotes tissue repair and inhibits SARS-CoV-2 replication. ABX464 is designed to bind to the Cap Binding Complex, allowing the splicing of a non-coding RNA, LncRNA 205, to produce miR-124, a potent anti-inflammatory microRNA designed to prevent the translation of multiple chemo- and cytokines.
2021 Status: miR-AGE Trial Halted—Abivax said March 5 that it was halting the Phase IIb/III miR-AGE trial (ABX464-401; NCT04393038) in high-risk COVID-19 patients at the recommendation of the study’s independent Data Safety and Monitoring Board (DSMB) due to lack of efficacy. The DSMB recommendation followed a planned, interim analysis evaluating data of 305 high-risk COVID-19 patients who completed the study period. The comparison of the data generated in the patient group treated with ABX464 versus the placebo group, did not show a difference in the rate of severe disease between the placebo group and the ABX464 group. ABX464 was well tolerated and safe in these high-risk COVID-19 patients, Abivax added.
The trial had already recruited 500 high-risk COVID-19 patients out of the planned 1,034, and had been declared a “Research National Priority” by the French government in December 2020.
2020 Status: Abivax said July 2 that that the first patient had been treated with ABX464 in a Phase IIb/III study assessing COVID-19 patients at the University Hospital Center in Nice, France (CHU Nice).
The randomized, double-blind, placebo-controlled pan-European COVID-19 trial, called miR-AGE (NCT04393038), is designed to investigate early treatment with the drug at diagnosis in 1,034 COVID-19 elderly or high-risk patients. The trial’s main goal, according to Abivax, is is to assess the potential of ABX464 to block viral replication in these patients, as well as the severe inflammation that leads to acute respiratory distress syndrome (ARDS).
The study is also intended to evaluate whether ABX464’s triple mode of action proves effective against COVID-19: Preventing and reducing inflammation, as shown against ulcerative colitis, where the drug is in Phase IIb study; reducing viral replication; and promoting tissue repair and decreasing pulmonary fibrosis, Abivax added.
First top-line results from miR-AGE are expected by year’s end.
Abivax said June 15 it received €5 million ($5.6 million) in non-dilutive financing from Société Générale in the form of a loan guaranteed by the French state.
In May, Abivax won approval from the German regulatory agency for drugs and medical products, BfArM (Bundesinstitut für Arnzeimittel und Medizinprodukte), for a Phase IIb/III study of ABX464 in COVID-19 patients. The randomized, double-blind, placebo-controlled pan-European COVID-19 study, called the miR-AGE trial (NCT04393038), is designed to investigate early treatment with the drug at diagnosis in 1,034 COVID-19 elderly or high-risk patients. The trial’s main goal, according to Abivax, is is to assess the potential of ABX464 to block viral replication in these patients, as well as the severe inflammation that leads to acute respiratory distress syndrome (ARDS). The study is intended to evaluate whether ABX464’s triple mode of action proves effective against COVID-19: Preventing and reducing inflammation, as shown against ulcerative colitis, where the drug is in Phase IIb study; reducing viral replication; and promoting tissue repair and decreasing pulmonary fibrosis.
On May 15, Abivax was awarded up to €36 million (about $39 million) in non-dilutive funding by the French public investment bank Bpifrance toward its Phase IIb/III miR-AGE trial evaluating ABX464 in high-risk patients with COVID-19, as well as manufacturing scale-up and additional clinical and other development costs. The funding consists of €20.1 million (about $22 million) in grants and €15.9 million (about $17 million) in refundable loans, which Abivax would repay after ABX464 reaches commercial stage.
A day earlier, Abivax said ABX464 inhibited replication of SARS-CoV-2 in an in vitro reconstituted human respiratory epithelium model, as assessed by Transepithelial electrical resistance and RTqPCR. Also on May 14, Abivax won approval from France’s National Agency for the Safety of Medicines (ANSM) and French Ethics Committee (CPP) for the miR-AGE clinical trial.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types:
● ANTIVIRAL
● VAX
● ANTIBODY
● RNA
