Aridis' monoclonal antibody fails PhIII, but plans for second trial anyway
Aridis Pharmaceuticals’ monoclonal antibody missed the bar in a Phase III test in ventilator-associated pneumonia caused by the gram-positive bacteria S. aureus, the company announced Wednesday.
But Aridis is planning for a second Phase III study anyway once it discusses the findings with the FDA and the European Medicines Agency. Execs blamed recruitment challenges stemming from Covid-19 and Russia’s invasion of Ukraine for the miss, cutting their enrollment target in half.
“Despite the limitations of sample size and lack of statistical significance in the primary endpoint, we are pleased to see the clinical benefit trends across the study population,” Hasan Jafri, Aridis’ CMO, said in a statement.
Aridis’ antibody, AR-301, combined with antibiotics, failed to meet the primary endpoint on increasing the clinical cure rate at day 21 compared to antibiotics alone. The clinical cure rate at day 21 was 68.9% (42 of 61 patients) for AR-301 plus antibiotics versus 57.6% (34 of 59) with just antibiotics. The endpoint was reaching a 10% or more improvement compared to the control arm. While there was an 11.3% difference between the arms, the result was not statistically significant (p=0.23).
Zooming into subgroups gives a brighter picture — but still not in a statistically significant way. In adults 65 years and older, Aridis notes an absolute efficacy on day 21 of 34% (p=0.057) which increased to 38% on day 28 (p=0.025), largely because antibiotics are less effective for this group of patients. A similar finding was reported for methicillin-resistant S. aureus (MRSA) patients — the absolute efficacy was 28% higher than antibiotics alone due to the lower efficacy of antibiotics in MRSA patients (p=0.774).
However, Aridis claims better data on secondary endpoints, including “trends in reduction” for duration of hospitalization, amount of time in the ICU and days on ventilation.
There were no serious adverse events linked to the drug and none of the deaths in the study were deemed drug-related, the company says. The study enrolled 120 patients who had S. aureus as the predominant cause of pneumonia, down from the original goal of 240. Shares $ARDS tumbled more than 30% to $0.84.
AR-301 targets S. aureus alpha-toxin, which is secreted by the bacteria, with the hope of adding an additional layer of defense.
This is not the only one of Aridis’ antibodies for pneumonia to struggle. In 2019, the antibody AR-105 failed to beat out a placebo in treating ventilator-associated pneumonia caused by gram-negative Pseudomonas aeruginosa. And there was an imbalance in deaths and serious adverse events that left the therapy with a worse safety profile.