CFF Awards $3.3M to Advance Inhaled Antibiotic for Resistant P. aeruginosa Infections

The Cystic Fibrosis Foundation (CFF) has awarded up to $3.3 million to Polyphor AG to advance the testing of an inhaled version of murepavadin, an antibiotic that targets multi-drug resistant Pseudomonas aeruginosa infections in people with cystic fibrosis (CF).

According to a CFF press release, the funding will specifically support a Phase 1b/2a clinical trial of inhaled murepavadin in adults with CF. The trial is expected to start in the fourth quarter of 2021, following a study of the treatment’s safety in healthy volunteers.

P. aeruginosa is an opportunistic pathogen — an organism that commonly lives in the human body without causing health problems but that, in certain instances, can cause disease. The bacteria are the most important pathogen in progressive and severe CF lung disease, playing a central role in many CF lung infections.

Bacteria can evolve mechanisms that enable them to survive treatment with antibiotics that work to kill them. Those that do are commonly referred to as drug-resistant bacteria. Multi-drug resistance refers to bacteria that have evolved to resist different types of antibiotics.

Approximately 17% of all CF patients with P. aeruginosa infections in 2019 were infected with multi-drug resistant strains of these bacteria, the CFF reported.

Murepavadin is an Outer Membrane Protein Targeting Antibiotic (OMPTA), a type of antibiotic with a novel mode of action that was discovered by researchers at Polyphor and the University of Zurich. It works by disrupting the bacteria’s outer membrane, which is fatal for bacteria. Murepavadin has shown efficacy against a variety of P. aeruginosa strains in preclinical testing.

Because of its specific mechanism of action, it is thought that murepavadin will kill P. aeruginosa but will not have much effect on other bacteria types. This sets the OMPTA apart from broad-spectrum antibiotics which, as the name implies, kill many different types of bacteria.

OMPTA’s specificity may lessen the selective pressure that helps to spur the evolution of resistance mechanisms. It may also allow the eradication of disease-causing bacteria without substantially affecting bacteria that are beneficial for health.

Murepavadin is currently designed for intravenous (into-the-bloodstream) injection. An inhaled formulation could make it easier to specifically target the lungs and potentially allow at-home administration.

“A significant number of people with CF have multi-drug resistant strains of Pseudomonas each year that require IV [intravenous] antibiotics and hospitalization,” JP Clancy, MD, vice president of clinical research at the CFF, said in the release. “We hope to determine if the inhaled version of this new medicine could provide an alternative treatment option for people with CF that could potentially reduce their treatment burden.”

The CFF has set aside at least $100 million for its Infection Research Initiative, an 2019-23 effort to advance research into treatments for infections in people with CF. The foundation is currently funding 13 new industry programs into potential treatments for CF-associated infections. Additional information about CFF funding opportunities can be found here.