Treatment for antibiotic resistant lung and urinary tract infections
The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for AB569 in the treatment of Pseudomonas aeruginosa (P. aeruginosa) pulmonary infections in patients with cystic fibrosis.
Treatment for Respiratory Pseudomonas aeruginosa Infections
Two deadly diseases, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), are characterized by airway bacterial infections that significantly impact the overall quality of patient’s lives. There are approximately 40,000 CF patients and some 14.2 million individuals diagnosed with COPD in the United States. In both diseases, the Gram-negative bacterium, Pseudomonas aeruginosa (P. aeruginosa), constitutes a significant and problematic cause of the pulmonary exacerbations that result in frequent hospitalizations of these patients.
In particular, the mucoid form of P. aeruginosa is a very challenging infection to treat due to its high resistance to both antibiotics and phagocyte–mediated killing. Once patients present with the mucoid form of P. aeruginosa, their overall lung function precipitously declines resulting in a poor prognosis.
CF patients are predisposed to lung infections due to abnormal mucus production in the lungs and airways. P. aeruginosa infects 40% of CF patients between the ages of 6 and 10 years of age. By the age of 17, the frequency of infection increases to 60% and reaches approximately 75% of all CF patients between the ages of 25 and 34. Thus, there is an urgent clinical need for the development of novel effective treatments in this area.
AB569 constitutes an innovative, bactericidal method to treat mucoid and nonmucoid P. aeruginosa pulmonary infections that are resistant to traditional antibiotics.
Human Trial Plans
The Cincinnati Veterans Affairs Medical Center (CVAMC) will conduct an investigator initiated Phase I human trial to evaluate the safety and pharmacokinetic profile of AB569, Arch Biopartner’s inhalation drug candidate for treating antibiotic-resistant bacterial infections in the lungs.
According to WHO, while there are new antibiotics currently in development, none are expected to be effective against the most dangerous forms of antibiotic-resistant bacteria. The Company’s AB569 is a non-antibiotic drug that could be a viable alternative or adjunct therapy to current standard of care antibiotics.
AB569 consists of two active ingredients, sodium nitrite and ethylenediaminetetraacetic acid (EDTA) that have potent, synergistic bactericidal properties. AB569 has a novel mechanism of action that differs from that of antibiotics and was invented by Dr. Daniel Hassett at the University of Cincinnati College of Medicine.
In pre-clinical studies, Dr. Hassett and his team demonstrated the potency of acidified sodium nitrite and EDTA in killing drug resistant bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia under both aerobic and anaerobic planktonic (free-living) and biofilm (surface-attached) conditions. These bacteria are among the most common pathogens to chronically infect the lungs of patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF).
“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. 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,” said Dr. Hassett.
Dr. Ralph Panos, Chief of Medicine at CVAMC and world-renowned COPD expert, is the lead investigator of the trial. Arch is funding the study, contributing AB569 inhalation kits and other materials to support the trial.
“This is an important trial to show clinicians that AB569 is safe for use in humans. 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. Greater than 40% of patients at the CVAMC have COPD and AB569 has the potential to solve a major clinical challenge we currently face,” said Dr. Panos.
Clinical investigators at the CVAMC will evaluate single administration of nebulized AB569 in normal participants. The Phase I trial has been designed to determine the pharmacokinetic profile of plasma nitrite and nitrate metabolites, exhaled nitric oxide and circulating hemoglobin after a single inhalation of AB569. In addition, the trial also aims to determine the tolerance of nebulized AB569 in three escalating doses of acidified sodium nitrite and EDTA.
“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, a board member of Arch.
Dr. Hassett’s team has also shown the potential of AB569 to be used for treating drug resistant urinary tract infections and as an effective catheter lock solution to inhibit infection and destroy bacterial biofilms commonly observed in dialysis patients.
The Company’s sponsorship of the human trial application to the Internal Review Board of CVAMC and University of Cincinnati was facilitated through the Cincinnati Education and Research for Veteran’s Foundation.
As a result of the approved Phase I human trial at CVAMC, Arch has initiated the GMP manufacturing of the AB569 drug product that is required for the trial. It is expected that the Phase I trial will be ready to start once the drug kits are completed and delivered to CVAMC.
Orphan Drug Designation for AB569
In November, 2015, Arch Biopartners received Orphan Drug Designation on AB569 from the U.S. Food and Drug Administration for the treatment of P. aeruginosa lung infections in cystic fibrosis (CF) patients.
The Orphan Drug Designation has been granted for the combination of two active ingredients of AB569: sodium nitrite and ethylenediaminetetraacetic acid. AB569 is to be administered to patients as a nebulized (inhaled) solution. AB569 was invented at the University of Cincinnati in the lab of Dr. Daniel Hassett.
The FDA Office of Orphan Products Development grants Orphan Drug Designation to drugs and biologics to encourage the development of new medicines for the safe and effective treatment of underserved, rare diseases or disorders that affect less than 200,000 patients in the U.S.
The Orphan Drug Designation qualifies Arch for a seven-year term of market exclusivity to sell AB569 in the U.S. following FDA approval of the drug. Additionally, as Arch takes AB569 through the regulatory and human trial process, the Orphan Drug Designation provides an accelerated review and approval process, potential grant funding, tax benefits and an exemption from certain user fees.