The use of viruses to treat bacterial infections has great potential, but it still faces challenges. To shed light on the state of the field, GEN consulted Martha Clokie, PhD, professor of microbiology at the University of Leicester. She is also the editor in chief of PHAGE: Therapy, Applications, and Research, a peer-reviewed journal published by Mary Ann Liebert, Inc.
GEN: How would you describe the current state of phage therapy research?
Clokie: There is currently significant interest throughout the world in bacteriophages (phages), which has been motivated by a need for novel antimicrobials. Although phage therapy research is still at an early stage in the West, it has a long history in the Republic of Georgia and in other parts of Eastern Europe.
Several early-phase clinical trials are currently in progress. For example, BiomX, an Israeli company, recently released data from a Phase Ia trial using phages to target patients with high numbers of Klebsiella pneumoniae associated with inflammatory bowel disease and primary sclerosing cholangitis. The company showed that these patients had elevated numbers of phages in their stool samples, and that the phages were indeed amplifying in situ.
Moreover, increasing numbers of patients are being treated compassionately. For example, doctors together with phage researchers at Yale University have successfully treated tens of patients with multidrug-resistant lung infections. With expansions in collaborations, data acquisition, funding, and trials, I anticipate that phage products will be on the market within the decade.
GEN: What factors have been most responsible for the success of this approach?
Clokie: The factors are the phages! They have a long history of being used in therapy.
In general, the worsening antimicrobial resistance crisis is driving the recent successes that have been achieved with phage therapy. The compassionate data are compelling. In addition, work in animal trials is showing efficacy, and this can inform human trials. In addition, we can now explore and exploit phage genomes to assist phage development.
GEN: What remain as obstacles?
Clokie: The main obstacle is the scarcity of clinical trial data. As for any new drug, trials need to be resourced, and they are expensive.
Regulation and production are also problematic. There are regulatory complexities associated with phages because of the way they replicate and encode for genes of unknown properties. In addition, production at scale is difficult because few facilities produce GMP [Good Manufacturing Practice] phages at that level.
Scientifically, it is hard to compare different phages and establish which are the best for therapy. Also, it is difficult to find phages for many bacterial species. Although phages have huge potential, there is a lot of fundamental science and clinical trial work that remains to be done before phages become part of the established treatment of infection.
GEN: How will the roadblocks facing phage therapy be overcome?
Clokie: Fortunately, most of the roadblocks are in the process of being removed. Trials are being supported by a mixture of industrial and government funding. Regulators of medicinal products across the globe—such as the FDA in the United States and the MHRA in the United Kingdom—are becoming increasingly engaged and informing phage researchers what data they need to collect to develop a product. And companies are starting to produce phages to GMP standards and to learn how to scale this process.
Importantly, in terms of the science, more partnerships are springing up between phage researchers and doctors at the front end of patient care. Such relationships will ensure that optimal phages are developed.
Furthermore, compassionate care data are being collected in a more systematic way. For example, Shawna McCallin, PhD, clinical coordinator at the Balgrist University Hospital, has been setting up a registry to assist in the uniform collection of data from compassionate care cases.