Patients’ access to lifesaving treatments using bacteria-targeting viruses known as bacteriophages is increasing in the United States as developers gradually gain approval from the U.S. Food and Drug Administration (FDA).
Bacteriophage treatment, or “phage therapy,” targets specific infectious bacteria resistant to antibiotics, while leaving good bacteria in the body unharmed.
Developers working with the U.S. Navy used phages to cure a patient infected with multidrug-resistant bacteria, according to a press release by co-developer AmpliPhi Biosciences Corporation, which presented the success story at the Centennial Celebration of Bacteriophage Research at the Institut Pasteur in Paris on April 26.
FDA’s stringent testing process heavily restricts the use of phage therapy for human patients, prompting some U.S. patients to obtain treatment in other countries.
FDA allows the use of phages to sterilize foods containing potentially harmful bacteria.
FDA: Do It Yourself?
Dr. Robert Schooley, who treated the patient in the AmpliPhi case, says phage therapy could cure countless patients with antibiotic-resistant bacterial infections.
“Phage therapy could help tens of thousands of patients each year in the U.S. who have few or no other therapeutic options and, as a consequence, face severe disability or death,” Schooley stated in the AmpliPhi press release.
Chris Smith, CEO of Phage International, the San Francisco-based holding company of two bacteriophage treatment clinics in the Republic of Georgia, says regulations prevent U.S.-based doctors from prescribing phage therapy but allow patients to try phages themselves.
“Phages are not FDA-approved,” Smith told Health Care News. “That’s why the treatment is not generally available. However, with a doctor’s letter stating they are aware the patient is importing phages for personal use, FDA actually does allow patients to import phages.”
Do-it-yourself phage therapy is unlikely to produce positive results, Smith says.
“It is important that the phages are properly selected and combined in order to end up with something that actually works,” Smith said.
Decades of Experience
Doctors have treated patients using phage therapy since the 1920s in countries formerly part of the Union of Soviet Socialist Republics (USSR), which funded the phage therapy-pioneering Eliava Institute in Tbilisi, Georgia, until the USSR collapsed in 1991.
Smith says FDA should give phage therapy room to grow, given the treatment’s safe track record.
“Since there are 100 years of use and it is known that bacteriophages do not affect tissue, it would be nice if the FDA would consider this and reduce the rigor of their studies required to use them legally in the United States,” Smith said.
Given leeway, developers could individually customize bacteriophage treatment for each patient, says Alexander Sulakvelidze, vice president of research and development and chief scientist at the biotech company Intralytix, Inc.
“The optimal efficacy could be achieved when phages are individually selected for each patient,” Sulakvelidze said. “The idea is feasible and was actually used in the former Soviet Union to some extent, but it will require some changes in both medical culture and equipment infrastructure to implement this in the United States.”
Eric Keen, a graduate student of molecular microbiology and microbial pathogenesis at Washington University in St. Louis, Missouri, says FDA clinical-trial requirements are unsuitable for testing individualized phage treatments.
“At its best, phage therapy is a form of personalized medicine because specific phages are carefully selected to treat a patient’s specific bacterial infection,” Keen wrote in the scientific journal Frontiers in Microbiology in 2012. “To date, the FDA has essentially grafted its traditional antibiotic regulatory protocols onto phage therapy. This policy does not reflect the fundamental differences between phages and antibiotics.”
Despite restricting phage treatment for patients, in 2006 FDA approved six individualized phages designed to attack listeria, a deadly bacterium hosted by meat and poultry products.
FDA approved the use of phages for food sterilization at the request of Intralytix, the agency website states. Intralytix has received FDA approval for four food sterilization products using phages.
Sulakvelidze says FDA has readily approved the use of phages on food, if not on patients.
“All discussions we have had with the FDA so far have been reasonable, and the agency seems to be interested in working with phage companies,” Sulakvelidze said. “The overall FDA policy can become a bigger issue later, after initial phage products are available, in order to enable optimal use of this platform, phage therapy.”
A good policy for the future would be for FDA to let developers fine-tune their approved phage-therapy products without subjecting them to new trials, Sulakvelidze said.
“It would make sense to develop a regulatory strategy that will allow companies to implement fast product updates—i.e., replacing ineffective phages in their cocktails with new phages effective against newly emerged resistant bacterial clones—without going through the entire approval process again,” Sulakvelidze said.
Keen says FDA should trust established bacteriophage science.
“If the FDA were to modernize its current stance on phage therapy, scientific certainties, not regulatory uncertainties, could determine the future of this promising treatment,” Keen writes.
Stephanie Wisner ([email protected]) writes from Ann Arbor, Michigan.
Michael McGrady, “Bacteriophage Therapy Grows as Alternative to Antibiotics,” Health Care News, The Heartland Institute, July 2016: https://heartland.org/news-opinion/news/bacteriophage-therapy-grows-as-alternative-to-antibiotics
Eric C. Keen, “Phage therapy: concept to cure,” Frontiers in Microbiology, July 2012: http://journal.frontiersin.org/article/10.3389/fmicb.2012.00238/full