Last week, our review on compassionate phage therapy was published in Viruses. Our goal with this review was to summarize compassionate phage therapy cases worldwide, outline the general process of compassionate phage treatment, and highlight areas in need of improvement.
For a digestible summary of the main points, please read on. If you’ve got more time, feel free to check out the full-length review!
Phage accessibility can help patients
In the best of worlds, phage products would be readily available for treatment of bacterial infections for patients in need. The way to achieving such accessibility is through marketing authorizations granted by health agencies, such as the FDA or EMA. These authorizations are granted based on sound results from clinical trials.
Not everyone has time to wait for phage clinical trials
None of the three trials for phage products completed to date have resulted in marketing authorizations, and there has not yet been a single phase lll trial. Only one phase ll trial is actively recruiting patients.
The reality is that phage products are at least several years out from attaining a marketing authorization, while antibiotic resistant infections continue to complicate and prolong treatments, or ultimately, take the lives of patients.
In the meantime: compassionate phage therapy
In the interim, compassionate use of phage therapy has been used increasingly frequently on a patient-to-patient basis, to varying degrees of success.
Our recently published review of compassionate phage therapy includes nearly 30 published reports, including >2000 patients where phages have been used to treat antibiotic resistant infections with different pathogens, via different administration routes, and in different countries.
The problem: reporting is scarce and variable
The variability between different clinical indications, results, and reporting criteria in these reports makes it nearly impossible to draw cumulative conclusions, but knowledge of how phages are being used in human therapy is undeniably important for its future development.
Information such as PK/PD data, bacterial load, adverse effects, beneficial combinations with antibiotics, or the appearance of phage-resistant variants can help to refine and improve treatment protocols, establish safety, and substantiate claims of antimicrobial activity.
No centralized reporting requirements for compassionate phage therapy
The fact is, however, there are currently no requirements for publicly reporting compassionate phage treatments, with many cases being published years later, or not being published at all.
Published reports range from thoroughly-investigated to second-hand accounts of the clinical result. It is also becoming more common for patient treatments to be announced via less formal channels of communication than scientific peer-reviewed journals, such as press releases and youtube.
A missed opportunity?
The question is then, is this lack of centralized reporting a missed opportunity, both for better patient treatment and for advancing phage therapy?
We argue that yes, a lack of formal reporting of case reports of compassionate phage therapy is a missed opportunity.
Increased reporting would create opportunities for more systematic comparison between cases, as well as to prevent biases for positive outcomes.
However, a balance needs to be struck between reporting and protecting the know-how of phage biotechs, while at the same time not compromising the true intention of compassionate treatment, which is to provide maximum benefit to the patient.
How do we put this into practice?
The questions that remain are the ‘who, where, what, and how’ about facilitating and encouraging compassionate phage use reporting. The reality is that while there have been many reviews and expert opinions addressing different aspects of phage therapy, these reviews and opinions rarely translate to actionable steps or policy changes. Indeed, we received an apt and appreciated comment from a reviewer on the lack of a practical formulation of our proposals.
Going forward, we are exploring possible actions we can take. One option is to make available a continually up-to-date list of compassionate phage therapy case reports. Ideally, with support from the phage community, we can collectively work toward creating a set of reporting standards for compassionate phage use.
McCallin, S., Sacher, J. C., Zheng, J., & Chan, B. K. (2019). Current State of Compassionate Phage Therapy. Viruses, 11(4), 343. https://doi.org/10.3390/v11040343