high 2.0 mg/kg dose (n=53), medium 1.0 mg/kg dose (n=56) or low 0.5 mg/kg dose (n=52) of Auxora or a matched dose of placebo (n=53) intravenously every 24 hours for a total of three doses.
Treatment and observation of patients continued for 30 days. CT scans to evaluate pancreatic inflammation and necrosis were performed at study entry and at 30 days. Patients were stratified by baseline hematocrit, a biomarker for inflammation
severity and were well-matched for all baseline characteristics with the exception that the placebo group had approximately 12% lower proportion of hyper-inflamed patients than the study overall.
Summary of Efficacy & Safety Data
In addition
to the topline data previously reported in June 2024, the Phase 2b CARPO trial met its study objective by showing clinically meaningful reductions for observed high and/or medium dose Auxora patients compared to placebo or combined placebo and low
dose Auxora patients in additional key endpoints including statistically significant reductions in rates of new-onset severe respiratory failure and new-onset persistent
respiratory failure, reductions in new-onset necrotizing pancreatitis, reduced times to medically indicated discharge and reductions in the proportion of patients requiring long hospital stays.
New onset severe respiratory failure, defined as (i) receiving invasive mechanical ventilation or (ii) use of either high-flow nasal cannula or non-invasive mechanical ventilation for 48 hours or longer, occurred in 0% of high dose patients, 0% of medium dose patients, 8.3% of low dose patients, and 8.5% of placebo patients, representing a 100% (p = 0.0027)
relative risk reduction when combined high and medium dose patients were compared to combined low dose and placebo patients. New-onset persistent respiratory failure, defined as (i) severe respiratory
failure or (ii) not severe respiratory failure but PaO2 /FiO2 of 300 or lower for 48 hours or longer and use of low-flow oxygen support, occurred in 8% of high dose patients, 1.9% of medium dose patients, 10.4% of low dose patients, and 17% of placebo patients, representing a 64.2% (p = 0.0476) relative risk reduction when
combined high and medium dose patients were compared to combined low dose and placebo patients.
Additionally, new onset necrotizing pancreatitis,
measured on day 30 occurred in 29.7% of high dose patients, 40.8% of medium dose patients, 38.6% of low dose patients, and 37.0% of placebo patients, representing a relative risk reduction of approximately 20% for high dose patients compared to
placebo patients.
Median time to medically indicated discharge, defined as (i) no clinical evidence of infection necessitating continued
hospitalization, (ii) solid food tolerance, and (iii) abdominal pain resolved or controlled with non-opiate medications, was 89.0 hours for high dose patients, 104.5 hours for medium dose patients,
109.5 hours for low dose patients, and 104.0 hours for placebo patients, demonstrating a reduction of 15.0 hours for high dose patients when compared to placebo. Long hospital stays were reduced in combined high and medium dose patients compared to
combined low dose and placebo patients, with 18% vs 31% of patients in the hospital longer than 7 days, 5% vs 10% longer than 14 days, and 1% vs 6% longer than 21 days, respectively. There were no high dose patients who stayed in the hospital longer
than 21 days.
When key endpointsall-cause mortality, new-onset
severe respiratory failure, new-onset necrotizing pancreatitis, and time to medically indicated dischargewere integrated into a win ratio analysis, the high dose of Auxora outperformed placebo by a
similar margin across all endpoints and delivered a stratified win ratio of 1.640 (p = 0.0372).
As in prior Phase 2 trials, Auxora provided patients with
clinically meaningful improvement and was well-tolerated. There was a trend of decreasing treatment emergent serious adverse event (TESAE) rates with increasing doses of drug. Additionally, there were no drug-related TESAEs or deaths in
patients receiving the high dose of Auxora.