The Promise of Bacteriophage Therapy Rekindled but Hurdles Remain

Antibiotic resistance is a mounting public health concern with the  CDC estimating the annual added cost of treating antibiotic-resistant infections at $20 billion in the US alone. The CDC also estimates that 50-70% of hospital-acquired infections are now resistant to first-line antibiotics. Given the dearth of new classes of antibiotics, drug companies are looking at non-traditional approaches such as bacteriophage (phage) therapy to compete in this market. Phages are naturally occurring viruses that consume bacteria by hijacking their metabolic processes to replicate before rupturing the host cells to release new viruses. Once all bacteria have been destroyed, the phage is cleared harmlessly by the body. The appeal of phage-therapy lies in its specificity to particular bacterial strains and much lower incidence of resistance. Individual components of a cocktail can also be tweaked in response to the development of resistance. This approach allows targeted monotherapy that spares a patient’s commensal flora, as well as cocktail-therapy to target a broader spectrum. While their antibacterial utility has been known for over 100 years, phages were upstaged by antibiotics in the West, although research and use continued in the former Eastern Bloc countries. Progress in the West has continued to be slow despite the  FDA approving the use of phages in food products back in 2006. But according to an
 article in the current issue of Nature Reviews Drug Discovery, this looks to change with a  phase I/II trial of two phage products in a critical-care setting of 220 burn patients scheduled to begin this past July, and another study testing a topical phage product for the treatment of wound and skin infections caused by Staphylococcus including MRSA strains set to begin later this year in US army facilities. A biotech startup also earned FDA approval last year to start clinical testing of a phage product for diabetic foot ulcers. Still, significant regulatory hurdles remain. There is the question of patentability since phages are naturally occurring. This issue appears manageable through trade secrets and confidentiality agreements along with creative patents that cover therapeutic aspects such as phage composition, genetic modifications and combination panels with other agents. It is also unclear whether new clinical trials would need to be conducted every time the individual components of a cocktail are tweaked to overcome the development of resistance. The general feeling amongst industry stakeholders is that there is likely to be some flexibility on the part of regulators, but the landscape will really begin to take shape once clinical trials have formally proved the efficacy of phage therapy. Given the renewed interest in this therapeutic approach, and the new policy  initiatives under the Generating Antibiotic Incentives Now Act (GAIN Act), it shouldn’t be long before there is a clear indication of how regulators view this technology.