Phase III AR-301-002 study of AR 301 shows improved clinical cure rate in pneumonia infection.- Aridis Pharma

AR-301-002, the first of two planned Phase III studies, enrolled 174 mechanically ventilated intensive care unit (ICU) patients who were likely to have pneumonia caused by S. aureus, with 120 of those patients ultimately meeting the criteria of S. aureus as the predominant cause of pneumonia (microbiologically evaluable Full Analysis Set [micro-FAS]), being evaluated for efficacy. The COVID-19 pandemic and the subsequent conflict in Eastern Europe limited patient enrollment from the original target sample size of 240.

Primary outcome measures of efficacy compared clinical cure of AR-301 + SOC vs. SOC alone at Day 21 post-treatment: An improvement in clinical cure rate (or absolute efficacy) of ?10% (considered a clinically meaningful improvement by many key opinion leaders) was observed with adjunctive use of AR-301. However, with the limited sample size evaluated, statistical significance was not reached for the primary endpoint of clinical cure rate on Day 21 compared to antibiotics alone. Clinical cure at Day 21 was 68.9% (42/61 patients) for AR-301 + SOC versus 57.6% (34/59) for SOC alone, (efficacy difference or absolute efficacy: 11.3%, [p= 0.23]). In the prespecified older adult population of 65+ years, the absolute efficacy (improvement in clinical cure rate) on Day 21 was increased to 34% (p= 0.057), and to 38% on Day 28 (p= 0.025). The increase in absolute efficacy was driven primarily by the lower efficacy of SOC antibiotics in older adults 65+ years old compared to adults less than 65 years old (30% vs. 75%, respectively). In the methicillin resistant S. aureus (MRSA) patients, the absolute efficacy was 28% higher than SOC alone (p=0.774). The increase in absolute efficacy was also driven primarily by the lower efficacy of SOC antibiotics in MRSA patients compared to methicillin susceptible S. aureus (MSSA) patients (38% vs. 63%, respectively). Treatment with AR-301 was associated with reduction trends in key secondary outcomes measures of duration of hospitalization (median 19 vs. 28 days, difference: 9 days) time in ICU (median 13 vs. 20 days, difference: 7 days) and mechanical ventilation days (median 6 vs. 8 days, difference: 2 days). Consistent positive efficacy trends were observed in favor of AR-301 treatment in other key secondary efficacy outcomes (e.g. clinical cure at days 7, 14, 28).

Primary outcome measures of safety and tolerability of AR-301 were achieved. AR-301 intravenous (IV) infusion was well tolerated. Adverse Events (AEs) and Serious Adverse Events (SAEs) reported over the 28-day study period for the single IV infusion were similar across the active and placebo treatment groups, with no SAEs deemed drug-related. None of the deaths in the study were deemed drug-related by the blinded investigators. The independent unblinded Data Safety Monitoring Board (DSMB) also did not express any safety concerns. The all-cause mortality rates in all patients were AR-301: 23.6% (21/89) vs. SOC: 18.8% (16/85) (p=0.367); these deaths were primarily associated with patients’ underlying conditions which brought the patient into the ICU. The all-cause mortality in the evaluable microFAS population were similar between the AR-301 23.0% (14/61) and placebo 23.7% (14/59) groups (p=0.830). The mortality due to pneumonia was: AR-301 1.6% (1/61) vs SOC 5.0% (3/59) groups among the population with confirmed S. aureus pneumonia (p=n.s.).