ABIONYX Pharma reported that the pilot Phase 2a clinical trial evaluating CER-001, the only natural recombinant apoA-I, as a treatment for septic patients at high risk of developing Acute Kidney Injury (AKI) met its primary objective. There are no approved treatments for septic patients in the world. The RACERS study included 20 patients with gram-negative sepsis who were at high risk for acute kidney injury due to high levels of endotoxin activity and decline in function of one or more organ systems. Patients received either standard of care treatment alone, or in combination with one of three dosage regimens of CER-001 (five patients per group).

The main objective of this pilot study was to investigate whether the use of CER-001 at different doses, in combination with standard of care (SOC) treatment, is safe and effective, providing a potential new strategy to treat septic patients, reducing the inflammatory response to endotoxin and preventing the progression to AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria, as well as safety and tolerability of the dosage regimens in order to select the optimal dose of CER-001. One of the metabolic characteristics of bacterial (like sepsis) or virus infections (like sars-Cov-2) is the strong decrease of circulating lipoprotein and particularly the High-Density Lipoprotein (HDL) with its main containing protein apolipoprotein A-I (apoA-I). As an example, apoA-I level was recently described as the biomarker predictive of long-term mortality after surgical sepsis1.

The rational of Abionyx was to restore, using CER-001, the apoA-I levels to reestablish all the functionality of this individualized biomarker leading to potential benefit in sepsis pathology. RACERS pilot study has shown for the first time in a human pilot trial that the recovery of a normal apoA-I level in patient stop the cytokine storm and improve the clinical outcomes. CER-001 demonstrated rapid and sustained reduction in endotoxin levels and consequent reduction in the inflammatory cascade or “cytokine storm” relative to SOC alone.

Endothelial biomarkers demonstrated a significant protective effect of CER-001. Trends towards fewer ICU days, lower requirement for organ support and improved 30-day survival. Evaluation of safety data, taken together with the pharmacokinetic and pharmacodynamic data, has identified the dose that will be used in subsequent studies.

The observed safety and efficacy in RACERS were generally consistent with historical data including clinical results for CER-001 in COVID-19 that were published recently in the scientific journal "Frontiers in Medicine", a specialty medicine journal, in September 2022. The potential use of CER-001 in septic patients is currently under clinical development. These data will be discussed with regulatory authorities, starting with Europe but also the U.S. later this year in order to design an appropriate clinical and regulatory development strategy for this disease state that currently has no available treatment options.

RACERS is a clinical trial named RACERS (a RAndomized study comparing short-term CER-001 infusions at different doses to prevent Sepsis-induced acute kidney injury) with CER-001 in septic patients at high risk of developing acute kidney injury. Following the positive signals observed in the Temporary Authorization for Named Use (ATUn) in an ultra-rare kidney disease, the study assessed the role of CER-001, a novel, in preventing Acute Kidney Injury (AKI) in septic patients. The core component of the program is the launch of a 30-day Phase 2a clinical dose-finding trial with the Company's lead product candidate, CER-001, in the prevention of AKI in septic patients.

Researchers have demonstrated that in humans, reconstituted HDLs have a scavenger role in reducing circulating endotoxin, as well as major anti-inflammatory and endothelial activity. These important effects were also demonstrated with CER-001 in a rigorous preclinical model of sepsis-induced AKI developed in collaboration with an Italian Veterinarian Hospital (Surgical Section, Chief: Prof. Antonio Crovace). Several other AKI/sepsis models showed that HDL is a critical factor in modifying the disease.

This clinical study, designed in concert with expert Italian nephrologists (Nephrology, Dialysis and Transplantation Unit, Chief: Prof. Loreto Gesualdo) and intensivists (Anesthesiology and Resuscitation Unit, Chief: Prof. Salvatore Grasso), was a randomized, open labelled, placebo-controlled, parallel-group study evaluating the safety and efficacy of intravenously administered CER-001 in patients with sepsis at high risk for AKI based on their endotoxin levels and Sequential Organ Failure Assessment (SOFA score). A total of 20 patients were randomized to receive 8 doses of CER-001 over 6 days on top of standard of care, or standard of care alone. The primary endpoint of the study was the onset and severity of AKI according to KDIGO criteria as well as safety and tolerability of the dosage regimens in order to select the optimal dose of CER-001.

The clinical study was partnered with the University of Bari.