So What’s Holding Up a 100 Year-Old Super Bug Killer?

By Ansis Helmanis.

According to the Centers for Disease Control (CDC), about 2 million people fall victim to antibiotic resistant infections annually in this country and 23,000 die from those infections.  CDC’s Director has expressed concern that soon there may be no effective treatment for the growing number of antibiotic resistant super bugs.

An effective non-antibiotic bactericidal treatment for humans does exist.  First proven effective in 1919, the treatment uses viruses (phages) to kill targeted pathogenic bacteria, even antibiotic resistant ones, while leaving good bacteria unharmed. The bacteria-specific killer viruses (bacteriophages) in effect work somewhat like monoclonal antibodies that target only specific cancer cells. 

Eli Lilly in the US and L’Oreal in France supplied phage-based treatments in the 1920s and 30s for patients suffering from bacterial infections caused by staphylococci, streptococci, and escherichia coli. Bacteriophage use and research continued in the former Soviet Union and its East Bloc countries after the West switched to antibiotics in the 1940s.  And it is still in use today in Russia, Poland and Georgia

Which raises the question as to why bacteriophages for human use are not commercially available in this country.

A contributing factor appears to be the lack of FDA guidance for the development of phage-based therapies for human use.  So far, only small to medium size biotechs have announced development plans and they need the guidance the most. So-called Big Pharma companies are conspicuous by their absence from phage-based development.

Phage pioneers, such as PhageTech (later Targanta) and Exponential Biotherapies that announced development plans for human use in the late 1990s, have switched to small molecule drug development. Others, such as Intralytix, opted to first bring bacteriophages to market as food additives and for in vitro diagnostic use.  Intralytex has MRSA-specific phages but will not enter the regulatory black box for human development.

Another factor may be an ingrained bias toward what is viewed as Soviet era medical practice. Regulators claim a lack of evidence as to the safety and efficacy of bacteriophage use in humans, despite 70 years of therapeutic use and published research in the former Soviet Union and its East Bloc countries - and a placebo controlled clinical trial with over 30,000 children suffering from dysentery conducted in Georgia in the early 1960s.  The incidence of dysentery was three times greater in the placebo control group.

The only EU member state where bacteriopghage treatment is available, the former East Bloc country Poland, is on the sidelines of the first multi-center phage-based clinical trial launched in Europe. The contract for running the European Commission supported Phagoburn study went to two French biotechs, Pherecydes Pharma and Clean Cells.  And the clinical sites where the multi-center trials will be conducted are located in France, Belgium, and Switzerland – countries with no phage-based clinical experience.

Clearly there is no question that bacteriophages are effective. The issues blocking commercialization should not block access to phage-based therapies for those suffering from life threatening antibiotic resistant bacteria. They do not have the luxury of time to await the outcome of well-controlled multi-center clinical trials.

FDA should work with companies with phage-based pipelines to implement compassionate use access for those patients.  Moreover, given the limited pipeline that may be available today, the agency should also allow the import of patient-specific bacteriophage treatments from recognized overseas sources such as the Eliava Institute in Georgia, which is providing such treatments for European patients.

Ansis Helmanis, Special Counsel, is a Principal at RegLink News