ABX464 for COVID-19

Antiviral, anti-inflammatory and tissue repair properties

ABX464 is an oral, first-in-class, small molecule that has demonstrated safety as well as antiviral, anti-inflammatory and tissue repair properties in clinical trials in HIV and ulcerative colitis. New in vitro data show the inhibition of the replication of SARS-CoV-2 (COVID-19).

These characteristics make ABX464 the only drug candidate with the desirable and complementary triple action to effectively treat COVID-19 patients:

  1. Antiviral effect to inhibit the SARS-CoV-2 viral replication;
  2. Anti-inflammatory effect to prevent and treat the acute respiratory distress syndrome (ARDS);
  3. Tissue repair properties preventing longer-term pulmonary dysfunction.
COVID-19 disease

COVID-19 disease, caused by the SARS-CoV-2 virus, is a respiratory illness ranging from mild to severe. Elderly patients or patients with risk factors are more vulnerable to develop the severe and potentially deadly form of the disease. A so-called “cytokine storm” and hyper-inflammation syndrome, caused by the excessive production of multiple chemo- and cytokines, can be observed in the most severely ill patients. This leads to acute respiratory distress syndrome (ARDS), characterized by the acute onset of hypoxemic respiratory failure, requiring intensive care unit admission and oxygen therapy. The excessive production of these chemo- and cytokines needs to be hampered in order to avoid the occurrence of ARDS and thus reduce the severity of this disease.

Proven concept

ABX464’s antiviral effect

ABX464 showed the capacity to reduce or eliminate the viral HIV reservoirs in two Phase 2a clinical trials. This antiviral effect has now also been shown in the replication of SARS-CoV-2 (COVID-19), which was inhibited by ABX464 (magnitude similar to Remdesivir, the only drug currently approved in some countries for COVID-19 for emergency use) in an in vitro reconstituted human respiratory epithelium model. ABX464 could thus potentially deliver a reduction in the viral load of COVID-19 patients.

ABX464’s anti-inflammatory and tissue repair effect

ABX464 has demonstrated impressive efficacy in a Phase 2a trial in another severe inflammatory disease, ulcerative colitis, and its molecular mechanism of action supports the rationale to treat the cytokine storm and hyper-inflammation syndrome observed in COVID-19 patients. Hyper-inflammation in the lungs is the primary cause of the respiratory distress and death of COVID-19 patients. ABX464 has been shown to specifically upregulate a microRNA, miR-124, a “physiological brake” of inflammation. miR-124 down-regulates the multiple chemo- and cytokines that are involved in the COVID-19 cytokine storm, including TNF alpha, IL-1 beta, G-CSF, IL-6, MCP-1 and IL-17.

Moreover, ABX464 has also been proven to heal inflammatory lesions in ulcerative colitis patients. This means that COVID-19 patients may benefit from the anti-inflammatory effect of ABX464 and also from its tissue repair properties, to prevent potential longer-term pulmonary dysfunction following the infection.

To date, app. 400 patients have been treated with ABX464, and the drug candidate shows a very good clinical safety and tolerability profile along with evidence of superior long-term efficacy.

ABX464 triple effect

Interview with Prof. Hartmut Ehrlich on ABX464 indications and manufacturing collaboration

In the clinic

Due to the lack of an effective vaccine or treatment option and based on the potentially beneficial triple effect of ABX464 to reduce the severity of COVID-19 disease and to prevent ARDS, Abivax decided to expand its clinical trial program in the antiviral/anti-inflammatory field. Therefore, the Company has initiated a Phase 2b/3 clinical trial in high-risk COVID-19 patients.

The randomized and placebo-controlled trial will be conducted in 50 European and Latin American clinical trial centers in 1,034 high-risk patients (those older than 65 years or adults with risk factors). Patients will be treated with standard of care and take either 50mg ABX464 or placebo orally once daily for a duration of 28 days. Both hospitalized and non-hospitalized patients with confirmed COVID-19 disease can be enrolled in the study.

Main evaluation criteria

The absence of high-flow oxygen use, assisted ventilation or death within 28 days, as well as multiple clinical and biological secondary endpoints.

More information about this study can be found on clinicaltrials.com.