Investigational Phage Therapy for Cystic Fibrosis Multidrug Resistant Infections Shows 86.6% Resolution

One area of treatment that clinicians have struggled to get optimal outcomes is associated with patients who have cystic fibrosis (CF) and are colonized with Pseudomonas aeruginosa (P aeruginosa). The pathogen remains in the lungs of these patients, and over time, subsequent infections become more difficult to treat. It can have clinicians eventually running out of efficacious antibiotics and lead to severe consequences.

To learn more about the challenges of CF and P aeruginosa, read about one CF advocate’s experience with it.

One investigational treatment being examined in this area is bacteriophage (phage), and it continues to make inroads in small studies examining its effects on this multidrug pathogen. A recent development included a 15-person review study which demonstrated an 86.6% efficacy in using a specific phage treatment called PASA16 to resolve P aeruginosa infections in patients who were treated with the phage as either a standalone treatment or in combination with other therapies.

Gaithersburg, MD-based Adaptive Phage Therapeutics is a clinical-stage biotechnology company that developed PASA16, and began an early-stage clinical trial evaluating PASA16 in adults with CF who carry P aeruginosa in their lungs.

The results were published in Med. Adaptive worked with the Hadassah Medical Center in Jerusalem and they published the largest-ever study documenting the ability of a single virus, or phage, to kill a strain of antibiotic-resistant bacteria.

“Good clinical outcome was documented in 13 out of 15 patients,” the investigators wrote. “Two clinical failures were reported.”

According to the investigators, what makes this a unique study is that they were able to surmount the primary challenge in phage research, which is finding enough people infected with the same strain. Because it was able to make significant findings regarding such issues as quality control and dosing, the study will help researchers develop the protocols for the next round of phage research, which is clinical trials.

Does Phage Make Antibiotics Effective Again?

Clinical considerations going into it and safety of the patient is paramount. “Although [phage] cases are compassionate use, you want to keep some kind of conventional therapy...and you don't want to put them more at risk than they are,” said study investigator Ran Nir-Paz, MD, an associate professor of Medicine at the department of Clinical Microbiology and Infectious Diseases at Hadassah Hebrew University.

One of the ongoing, unexplained mysteries of phage is that it does assist in making antibiotics effective and can be used as a complementary therapy for patients with multidrug resistant infections.

“Sometimes the combination of antibiotics and phages have better outcome than phages alone, or antibiotics alone. And for many reasons, that while using phages, you keep the activity or reactivate the susceptibility of bacteria to the antibiotics,” Nir-Paz stated. “And also the other way around, so bacteria knows how to create resistance to phages; they have some kind of immunological mechanism. So you need to subvert this reaction of bacteria to phages—an antibiotic seems to help on that direction as well.”

Nir-Paz says the situation has complicated issues associated with using both therapies that need to be considered beforehand.

“In many cases, if you choose wisely, meaning you do some kind of simulation in the lab, or sometimes you do that just by trial and error, you use antibiotics and phages. And by that, you probably increase your ability to have a good outcome for your patients.”

Contagion spoke to Nir-Paz recently who offered insights on the development of the therapy, explained some of the clinical challenges to using phage, and what the likely next steps are for the investigational treatment.

Reference

Onallah H, Hazan R, Nir-Paz R, et al. Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series. Med. 2023;4(9):600-611.e4. doi:10.1016/j.medj.2023.07.002