The U.S. Food and Drug Administration gave positive feedback to the design of AmpliPhi Biosciences’ two proposed clinical trials of its Pseudomonas aeruginosa-targeting treatment candidate AB-PA01, the company announced in a press release.
P. aeruginosa is the major cause of lung infections in cystic fibrosis patients.
AB-PA01 is an investigational therapy based on bacteriophages, which are viruses that infect bacteria and are able to penetrate and disrupt drug-resistant bacterial biofilms — aggregates protected from the action of antibiotics. AB-PA01 was developed to specifically target P. aeruginosa and restore antibiotic sensitivity to drug-resistant bacteria.
Preclinical studies showed that AB-PA01 has a broad activity against 70-80% of global P. aeruginosa clinical isolates, and is able to significantly decrease their biofilms.
The two randomized, placebo-controlled Phase 1/2 trials will assess the therapy’s safety and effectiveness against P. aeruginosa-induced hospital-acquired and ventilator-associated pneumonia, and P. aeruginosa bacteremia — the presence of bacteria in the blood. Each trial will include about 100 patients. AB-PA01 will be administered by an infusion into the vein, combined with the best available antibiotic therapy.
Given the FDA’s general agreement with the design of the trials, neither additional data nor a type B pre-investigational new drug application meeting are required to proceed with the studies. The company will now seek financing to conduct the trials.
Resistant P. aeruginosa has been classified as “Priority 1: Critical” in the World Health Organization’s list of pathogens for which new antibiotics are urgently needed. In addition, multidrug-resistant P. aeruginosa was ranked as a “serious threat” by the U.S. Centers for Disease Control and Prevention.
“We are delighted with the FDA’s response to our development plans for AB-PA01,” Paul C. Grint, MD, AmpliPhi’s CEO, said in the release. “Additionally, I am strongly encouraged to see the FDA’s dedication to addressing the challenges of antimicrobial resistance [AMR] and promoting the development of new products, including bacteriophage therapeutics, as stated by the FDA’s Commissioner, Scott Gottlieb, at the unveiling of the FDA’s 2019 Strategic Approach for Combating AMR on September 14.”
“Pseudomonas aeruginosa is not only a challenging infection to treat, but one that represents a serious threat to the cystic fibrosis community as well as to lung transplant patients,” said Saima Aslam, MD, director of solid organ transplant infectious diseases services at the University of California San Diego School of Medicine.
“Having been involved in cases that have used emergency INDs to treat patients with investigational bacteriophage therapy, I welcome today’s news, as it has the potential to bring more widespread use of this treatment to the critically ill patients who could benefit from it,” she added.
Recently, a case report of a 26-year-old cystic fibrosis patient who had recurrent pneumonia and pulmonary exacerbations showed that treatment with AB-PA01 resolved the patient’s lung infection and was well-tolerated.