CalciMedica's novel CRAC channel inhibitor Auxora demonstrated significant mortality benefits in COVID-19 patients with acute kidney injury (AKI), according to new data presented at the 30th International AKI & CRRT Conference in San Diego. The findings, based on a post-hoc analysis of the Phase 2 CARDEA trial, showed a 62.7% relative reduction in mortality compared to placebo, persisting through 60 days of follow-up.
Striking Mortality Benefits in AKI Subgroup
The analysis focused on 38 patients who had both AKI (defined by eGFR ≤60 ml/min/1.73 m²) and moderate to severe respiratory failure. Among these patients, only 17.4% (4/23) receiving Auxora died by day 30, compared to 46.7% (7/15) in the placebo group - representing an absolute mortality reduction of 29.3%. This survival benefit exceeded the overall mortality reduction observed in the broader study population of 261 patients, where Auxora showed a 56.3% relative reduction (p=0.017).
Mechanistic Insights Support Therapeutic Potential
Dr. Sudarshan Hebbar, Chief Medical Officer of CalciMedica, presented compelling preclinical evidence supporting CRAC channel inhibition as a therapeutic approach for AKI. Key findings included:
- Reduced Th17 cells in kidney tissue of AKI rats treated with CRAC inhibitors
- Protection of podocyte cells from injury in high-glucose conditions
- Accelerated GFR recovery and reduced mortality in preclinical AKI models
- Favorable changes in cardiorenal biomarkers, including angiopoietin-1 increase and angiopoietin-2 decrease
Implications for Ongoing Clinical Development
"The biological rationale for CRAC channel inhibition as a potential therapeutic mechanism for AKI is compelling," noted Dr. Hebbar. The results are particularly relevant for CalciMedica's ongoing Phase 2 KOURAGE trial, which is evaluating Auxora in patients with Stage 2 or 3 AKI and acute hypoxemic respiratory failure.
The KOURAGE study represents a critical next step in Auxora's development program, with results expected in 2025. The trial builds on the promising signals observed in the CARDEA analysis, specifically targeting patients with both kidney and respiratory dysfunction - a population with significant unmet medical needs.
Safety and Therapeutic Window
Importantly, the data suggest Auxora provides a viable therapeutic window for treating acute critical illnesses without increasing infection risk at both experimental and clinical doses. This safety profile, combined with the observed efficacy signals, positions Auxora as a potentially valuable treatment option for critically ill patients with AKI.
