CalciMedica's Auxora Clears FDA Safety Review, KOURAGE Trial in AKI to Resume Dosing
Key Insights
FDA reviewed the KOURAGE trial protocol amendment and interim safety data for Auxora in acute kidney injury (search) patients and raised no comments or questions.
An earlier enrollment pause was triggered by a mortality imbalance that the IDMC and external experts attributed to baseline disease severity, not drug-related toxicity.
The protocol amendment refines patient inclusion criteria and stratification methodology based on a comprehensive safety assessment of 107 dosed patients.
CalciMedica announced that the U.S. Food and Drug Administration has completed its review of a protocol amendment and interim safety data from the Phase 2 KOURAGE trial evaluating Auxora (zegocractin) in patients with Stage 2 or Stage 3 acute kidney injury (search) (AKI) with associated acute hypoxemic respiratory failure (search) (AHRF). Following the applicable review period, the agency raised no comments or questions on the submission, clearing the way for the company to resume dosing patients in the study.
The development marks a significant milestone for CalciMedica, a clinical-stage biopharmaceutical company focused on calcium release-activated calcium (CRAC) channel inhibition therapies for serious inflammatory, immunologic, and cardiopulmonary diseases. The FDA's silence effectively confirms that the company may continue clinical development of Auxora across its pipeline of indications.
Trial pause and safety review
In January 2026, CalciMedica voluntarily paused enrollment in the KOURAGE trial following a recommendation from the trial's Independent Data Monitoring Committee (IDMC). The IDMC flagged a safety concern related to a mortality imbalance that warranted reevaluation of the study design. Critically, the IDMC did not identify evidence of drug-related toxicity, and the company's own comprehensive review, conducted in conjunction with external experts, reached the same conclusion. Instead, the review identified imbalances in patients' baseline disease severity that necessitated revisions to the protocol design.
In March 2026, CalciMedica submitted an amendment to address these design issues. The amendment included refinements to patient inclusion criteria and changes to stratification methodology, along with a comprehensive safety assessment of the 107 patients who had been dosed prior to the enrollment pause. This assessment incorporated cause-of-death information for all deaths and a detailed analysis of serious adverse events (SAEs). According to the company, the observed SAEs were consistent with previous clinical experience with Auxora and did not appear to be drug related.
Regulatory context
Because the KOURAGE trial was never placed on clinical hold — the decision to pause enrollment was made solely at the company's discretion — the FDA was not obligated to respond to the IND amendment. Nevertheless, after more than 60 days of review, the FDA's Clinical Pharmacology team within the Division of Cardiology and Nephrology confirmed it had no comments regarding the submission, and no clinical hold communication was issued.
Broader pipeline implications
The favorable regulatory outcome extends beyond the KOURAGE trial. CalciMedica expects to receive feedback from the FDA on the design of a potential pivotal program evaluating Auxora in acute pancreatitis (search) in the third quarter of 2026. Auxora has been evaluated in more than 350 patients across completed and ongoing clinical trials and is also planned for evaluation in a Phase 1b proof-of-concept study in patients with pulmonary arterial hypertension (search) (PAH).
Beyond Auxora, CalciMedica is advancing CM5480, a proprietary selective oral CRAC channel (search) inhibitor candidate, as a potential chronic oral therapy for chronic inflammatory diseases such as pulmonary hypertension (search). IND clearance for CM5480 is expected in mid-2027. Together, the two programs aim to establish CRAC channel inhibition as a differentiated therapeutic approach targeting both pulmonary vascular remodeling and right ventricular dysfunction in pulmonary hypertension.