FDA Grants Orphan Drug Status to AR-501, Potential CF Treatment for Chronic Lung Infections

AR-501, an investigational inhaled formulation of gallium citrate to treat chronic lung infections in patients with cystic fibrosis (CF), has been granted orphan drug status by the U.S. Food and Drug Administration (FDA).

The treatment, developed by Aridis Pharmaceuticals, is designed to be given once weekly and is self-administered within minutes, allowing a direct delivery to the lungs.

The safety and preliminary efficacy of AR-501 is currently being evaluated in an ongoing Phase 1/2 trial in healthy volunteers and CF patients with chronic lung infections due to Pseudomonas aeruginosa.

Orphan Drug Designation is granted to potential treatments that demonstrate promise for the diagnosis or treatment of rare diseases or conditions affecting fewer than 200,000 people in the U.S. This is meant to facilitate a therapy’s development to market and gives financial incentives for its clinical progress, including tax credits for clinical testing, waiver of certain FDA user fees, and potential eligibility for seven years of marketing exclusivity, if approved.

“We are pleased to receive the Orphan Drug Designation for AR-501. This candidate diversifies our portfolio of novel non-antibiotic anti-infective therapies and potentially provides a novel, convenient treatment option for cystic fibrosis patients to manage their chronic, life-long lung infections,” Vu Truong, PhD, CEO of Aridis Pharmaceuticals, said in a press release.

AR-501, also known as panaecin, is a non-antibiotic, inhalable form of gallium citrate. Gallium is a small molecule identical to iron, and is able to substitute for it in iron-dependent biological processes of bacteria. By starving bacteria of iron, gallium is believed to inhibit multiple bacterial pathways involved in infection and antibiotic resistance. According to Aridis, AR-501 mechanism of action is different from antibiotics, and it can also be effective against antibiotic-resistant bacteria.

Intravenous use of gallium citrate with traces of radioactive material is already approved by the FDA for use in medical imaging tests with diagnostic purposes, including PET scans to detect cancer.

Laboratory tests have shown that AR-501 has broad anti-bacterial activity against different strains of bacteria, including those resistant to antibiotics. It’s also been shown to improve the efficacy of antibiotics, and has a low resistance profile, which means that few bacteria are resistant to the agent.

In addition, data from a Phase 2 clinical trial (NCT02354859) demonstrated that intravenous injections of gallium are safe and can effectively improve the lung function of CF patients who had chronic infections. However, intravenous delivery involves a five-day continuous infusion, which is a demanding regimen.

AR-501 is more convenient as it can be self-administered and given once weekly, allowing for a direct delivery of gallium to the lungs, where infectious bacteria reside. The treatment’s safety and pharmacokinetics (the way it distributes in the body), along with preliminary efficacy, is currently under evaluation in a Phase 1/2a clinical trial (NCT03669614).

In Phase 1 part of the study, up to 48 healthy volunteers will be randomly assigned one of three ascending doses of AR-501, or a placebo, which will be self-administered using a hand-held nebulizer. The Phase 2a is expected to enroll up to 24 adult patients chronically infected by P. aeruginosa who will be assigned identical doses of AR-501, or a placebo.

During the trial, researchers will assess each participant’s changes in lung function and bacterial load in sputum following AR-501 administration.

The study is funded by the Cystic Fibrosis Foundation and led by Noah Lechtzin, MD, director of the Adult Cystic Fibrosis Program and associate professor of medicine at Johns Hopkins University.

Aridis expects to report data from the Phase 1 in the first quarter of 2020, and from Phase 2a in the second quarter of 2021.

Recruitment is still ongoing in Kansas. For more information, visit the official trial webpage here.