CalciMedica has reported top-line results from the Phase II CARDEA clinical trial of its lead drug candidate, Auxora, in severe Covid-19 pneumonia patients.
Auxora is an intravenous (IV) formulated small molecule that selectively inhibits the calcium release-activated calcium (CRAC) channel.
The drug hinders acute epithelial and endothelial cell injury and inflammation in organs, including the pancreas and lungs.
The randomised, double-blind, placebo-controlled Phase II trial enrolled 284 Covid-19 pneumonia patients who were in the hospital and receiving supplemental oxygen through a high flow nasal cannula or low flow device.
Initially, the company planned to enrol up to 400 subjects, but the enrolment was halted owing to the reduced number of Covid-19 cases and hospitalisations.
CalciMedica also attributed the halt to modifications in the standard of care (SOC) that comprised immunosuppressive therapies not included in the trial protocol.
The trial randomised 281 subjects in a 1:1 ratio to receive a minimum of one dose of either Auxora plus SOC or placebo plus SOC.
It had 261 subjects with moderate or severe respiratory failure and 23 participants with mild respiratory failure.
All subjects received SOC treatment with corticosteroids and more than 99% also received prophylactic anticoagulation treatment.
The time to recovery through day 60 was the trial’s primary goal.
In the 261-subject efficacy dataset, the median time to recovery was seven days for subjects in the Auxora arm versus ten days in the placebo arm, indicating a recovery ratio of 1.25.
In the 281-subject safety dataset, the median time to recovery was seven days for subjects receiving Auxora as against eight days in the placebo arm, signifying a recovery ratio of 1.30.
On the key secondary goal of all-cause mortality by day 60 and a supportive secondary goal of all-cause mortality by day 30 assessed in the 261-subject efficacy dataset, Auxora attained statistical significance.
In the Auxora arm, the 30-day all-cause mortality was 7.7% versus 17.6% for placebo, showing a 56% relative risk reduction and 9.9% absolute risk reduction for mortality.
The 60-day all-cause mortality was 13.8% in the Auxora group as against 20.6% in the placebo arm, indicating a 33% and 6.8% relative mortality risk reduction and absolute mortality risk reduction, respectively.
Findings also showed that Auxora was well-tolerated with a reduced proportion of 24.1% of subjects in the drug arm experiencing serious adverse events (SAEs) versus 35% in the placebo arm.
CalciMedica chief medical officer Sudarshan Hebbar said: “Initial efficacy signals for both time to recovery and mortality in CARDEA suggest that Auxora may rapidly reduce inflammation and reduce damage to vital organ tissue—both key in the fight against disease progression.
“These signals were observed even though we did not power the study for mortality endpoints, and we decided to halt enrolment before reaching our target.”
The company plans to discuss the trial results with the US Food and Drug Administration (FDA) and to assess additional opportunities to evaluate Auxora in Covid-19 patients.
In February, CalciMedica reported positive clinical data from the trial of Auxora in patients with severe Covid-19 pneumonia.