Arch Nears First Clinical Trial of AB569 as Treatment for Antibiotic-Resistant Lung Bacteria

Arch Biopartners is on the verge of its first clinical trial of AB569, an inhalation treatment for antibiotic-resistant bacteria that infect the lungs of those with cystic fibrosis (CF) and other pulmonary conditions.

The Phase 1 clinical trial, to be conducted at the Cincinnati Veterans Affairs Medical Center (CVAMC), will evaluate AB569’s safety and pharmacokinetics, or how it behaves in the body.

Antibiotic resistance is one of greatest threats to global health, the World Health Organization says. Some novel antibiotics are under development, but none seems to be effective against the most threatening forms of antibiotic-resistant bacteria, experts say.

AB569 may offer an alternative, or adjunct therapy, to current standard of care antibiotics. It is a non-antibiotic drug that targets Pseudomonas aeruginosa lung infections that are resistant to traditional antibiotics. AB569 combines two active ingredients: sodium nitrite and ethylenediaminetetraacetic acid, both of which have antibacterial properties.

Dr. Daniel Hassett of the University of Cincinnati College of Medicine (CVAMC) developed AB569.

Pre-clinical trial have shown that it kills drug-resistant bacteria such as P. aeruginosa, Staphylococcus aureus, and Burkholderia cepacia, which commonly infect CF patients’ lungs.

“My lab has shown AB569 to be very efficacious at killing all of the Gram-negative and Gram-positive bacteria strains we have collected over the years from numerous hospital patients, many of which are highly resistant to antibiotics,” Hassett said in a press release. “AB569 has demonstrated it can kill all of these bacteria in our in vitro studies at concentrations that do not harm human cells. Furthermore, we have discovered that none of these pathogens are capable of developing resistance to AB569.”

“This is an important trial to show clinicians that AB569 is safe for use in humans,” said Ralph Panos, chief of medicine at CVAMC and lead trial researcher.  “Once we establish that, we look forward to transitioning the AB569 program into a Phase II trial at CVAMC, where we can test the drug’s efficacy in treating antibiotic resistant infections in the lungs of patients with COPD [chronic obstructive pulmonary disease]. Greater than 40% of patients at the CVAMC have COPD, and AB569 has the potential to solve a major clinical challenge we currently face.”

The Phase 1 clinical trial will test a single administration of three doses of AB569 in healthy participants. The objective is to see how the participants tolerate the dose they received. The trial will also evaluate the pharmacokinetics of plasma nitrite and nitrate metabolites, exhaled nitric oxide and circulating hemoglobin.

“At a time where new treatments are urgently needed to kill highly problematic, antibiotic-resistant bacteria, moving AB569 into a Phase I human trial at CVAMC is a major milestone for the program and the development of Arch Biopartners,” said Claude Allary, an Arch board member.

Arch has begun making AB569 for the trial. The study will begin once its drug kits are delivered to CVAMC.

The U.S. Food and Drug Administration (FDA) granted Orphan Drug status to AB569 in 2015. The company has also applied for orphan drug designation from the European Medicines Agency.