AR-501 (Gallium Citrate): Novel anti-infective for the growing problem of antibiotic resistance
AR-501 is a novel small molecule anti-infective that diversifies our mAb immunotherapy-focused product portfolio. AR-501 is an inhalable form of gallium citrate, which acts as an iron analog to starve bacteria of iron. Gallium is believed to inhibit multiple iron-dependent synthetic and metabolic pathways required for pathogenicity. As with our monoclonal antibody programs, the mechanism of action of AR-501 is different from all antibiotics, and is effective against antibiotic resistant bacteria.
AR-501 has broad anti-bacterial activity against Gram-negative and Gram-positive bacteria in vitro, including antibiotic-resistant strains. AR-501’s inhibitory activity reaches bacteria growing in mature biofilms and prevents biofilm formation in viro. In mouse models of bacterial lung infections, a single inhalation exposure of aerosolized AR-501 protected the animal from morbidity and mortality. AR-501 was also protective when used in combination with antibiotics.
AR-501 is being developed as an inhaled treatment for the treatment of life-threatening bacterial lung infections in patients with cystic fibrosis (CF). Intravenously administered gallium was found to be safe and efficacious in a recent Phase 2 clinical trial involving cystic fibrosis patients (the study was conducted by Univ. of Washington). However, intravenous form of gallium involves a 5-day continuous infusion, which is a demanding treatment regimen for the patients. AR-501’s inhaled dosage form can be self-administered within minutes, designed to be given once weekly, and allows for direct delivery of gallium to the lungs where the infections reside.
It is currently being evaluated in a Phase 1/2a clinical study in healthy adult volunteers and cystic fibrosis adult patients. Safety data from the healthy adult population is expected in late 2019, followed by safety and efficacy data in cystic fibrosis patients in the second half of 2020.