AR-501, developed by Aridis Pharmaceuticals and also known as Panaecin, is an inhaled formulation of gallium citrate intended as a weekly and self-administered therapy delivered directly to the lungs. A non-antibiotic small molecule, it works by substituting for iron to starve bacteria of this mineral. This is believed to suppress several iron-dependent biological processes in bacteria, including those key to infection and antibiotic resistance.
Orphan drug status is granted to therapies aiming to treat life-threatening or chronically debilitating conditions that affect less than five in 10,000 persons in the EU. It provides financial incentives for clinical development, including reduced fees, protocol assistance from the EMA, centralized marketing authorization, and 10 years of marketing exclusivity after approval.
“Receiving orphan designation from the EMA for AR-501 is an important step in ensuring the program is well positioned from a global regulatory development pathway standpoint as we continue to advance its ongoing Phase 1/2a clinical trial,” Vu Truong, PhD, Aridis’ CEO, said in a press release.
AR-501 received a similar designation from the U.S. Food and Drug Administration (FDA) for the same indication in June.
An ongoing Phase 1/2a trial (NCT03669614) is testing the safety, pharmacological profile, and early efficacy of AR-501, first in up to 48 healthy volunteers, then in an equal number of CF patients with chronic lung infections due to Pseudomonas aeruginosa.
In both stages of the trial — funded by the Cystic Fibrosis Foundation — participants receive one of three increasing doses of AR-501, or a placebo, self-administered with a hand-held nebulizer. Measures of efficacy include changes in lung function and bacterial load in sputum up to 28 days after treatment.
Phase 1 results are expected in the first quarter of 2020, while those from Phase 2a are planned for the second quarter of 2021.
According to Aridis, preclinical tests showed that AR-501 is effective against antibiotic-resistant strains, improves the efficacy of multiple antibiotics, and has a low resistance profile, meaning that few bacteria are resistant to this agent.
An earlier Phase 2a trial (NCT02354859) showed that intravenous injections of gallium are safe, and improve lung function in CF patients with chronic infections. This study used a five-day continuous infusion of gallium, unlike the weekly and inhaled regimen in the ongoing trial.