CalciMedica said it is “moving quickly” to take Auxora into phase 3 after the calcium release-activated calcium channel inhibitor was shown to reduce the time before solid food could be consumed by a subgroup of patients with hyperinflamed pancreatitis.
The phase 2b CARPO trial enrolled 216 patients with acute pancreatitis (AP) and related systemic inflammatory response syndrome (SIRS) who received either a 2-mg/kg dose, a 1-mg/kg dose or a 0.5-mg/kg dose of Auxora or placebo intravenously every 24 hours for a total of three doses. Of these patients, 43% were identified as having hyperinflamed pancreatitis.
The trial hit the primary endpoint in this prespecified subgroup, according to CalciMedica, with even patients on the lowest dose showing a 1.5-day improvement on the 4.7 days that the placebo patients required before they could tolerate solid food again.
This effect increased to a 1.9-day improvement and a 2.1-day improvement in the high-dose and medium-dose drug cohorts, respectively.
While these changes were statistically significant, more than half of patients in the trial who didn't have hyperinflammatory AP didn’t show a measurable benefit. Instead, these patients were able to tolerate solid food “relatively quickly,” the biotech noted.
Still, CalciMedia said CARPO “met its study objective by showing a dose response for time to solid food tolerance as well as other clinical endpoints.”
“With these results, CARPO has added significantly to the body of evidence showing Auxora’s potential as an effective treatment for critically ill patients with acute inflammatory disease and warrants advancing our drug in both AP and acute kidney injury,” CalciMedica CEO Rachel Leheny, Ph.D., said in the release. “We plan to move quickly towards initiating our phase 3 trial in AP and are eager to engage with the FDA to discuss our trial plans once we have all the data from CARPO.”
The trial also proved a “statistically significant dose response in reduction” in severe organ failure, the company said. A total of 9.4% patients who received placebo suffered organ failure, a rate that was matched by the 9.6% of patients who received the lowest dose of Auxora.
But Auxora’s impact appeared to be demonstrated among the medium- and high-dose groups, of whom just 3.6% and 3.8%, respectively, suffered organ failure.
CalciMedica said the drug was well tolerated, with none of the 35 treatment-emergent serious adverse events (TESAEs) reported across the medium- and high-dose cohorts deemed as being drug-related, compared with one of the 23 in the low-dose group. Twenty TESAEs were reported in the placebo group.
Treatment-emergent adverse events led to the death of one patient in the placebo group and one in the medium-dose group, with no deaths occurring in the high-dose or low-dose group, the company said.
The biotech has already tested Auxora in COVID-19 patients during the pandemic and has another phase 2 trial ongoing in acute kidney injury. There is also a phase 1/2 trial in children with asparaginase-induced pancreatic toxicity as a side effect of leukemia treatment.