By Timo Minssen
Last week I blogged about recent publications concerning the global battle against anti-microbial resistance (AMR). I did not mention a recent paper published in the June 2014 issue of Nature, which describes how European and U.S. researchers and authorities are increasingly considering clinical research in unconventional areas to fight AMR. The news-report “Phage therapy gets revitalized” by Sara Reardon concentrates on the use of viruses (bacteriophages) to battle bacteria. The idea is not new, but apart from some applications in the former Soviet Union, it never was established as a major research area elsewhere. In particular the paper examines the European Phagoburn project, which is the first large, multi-centre clinical trial of phage therapy for human infections, funded by the European Commission. It involves a phase I-II trial of using viruses for the treatment of bacterial infection following burns. The European Union (EU) is contributing €3.8 million (US$5.2 million) to the Phagoburn study demonstrating that it is taking the approach seriously. Meanwhile, the US National Institute of Allergy and Infectious Diseases announced in March 2014 that it regards phage therapy as one of seven key areas in its strategy to fight antibiotic resistance.
So far Western practice has concentrated on treating complex or unidentified infections with broad-spectrum antibiotics. These antibiotics would typically eliminate multiple types of bacteria, including those who have beneficial effects to the human organism. Despite resulting in direct negative consequences for patients, e.g. gastrointestinal disorders, these “atomic bomb” approaches can result in biological niches where resistant “bad bugs” can prosper. This is the reason why scientists are turning towards more targeted approaches. This is where phage therapy comes into play. Like “guided missiles”, phage-therapy has the ability to kill just species of bacteria or strain. Quoting the US virologist Ryland Young and the head of the scientific council at the Eliava Institute in Tblisi (Georgia), Mzia Kutateladze, the Nature report explains how nature offers an almost unlimited source of different phages and that so far no identical phages have ever been found. For this reason it is fairly simple to identify a particular phage for a bacterial target. If the bacterium should become resistant against that particular phage, researchers would modify the viral cocktails that are used for treatment by adding or substituting phages. At the Eliava Institute such updates occur – according to the report – approximately every 8 months and the scientists would not be fully aware of the precise combination of phages in the cocktail.
In light of these advantages the recent interest of US and EU stakeholders in phage therapy comes as no surprise. However, the scientific and legal challenges confronting these projects are complex. After all we are talking about viruses here, which triggers alarm bells with regard to public perception, safety concerns, and the regulation of relevant research. It also appears questionable if – or under what circumstances – regulatory authorities would be willing to grant market approval for such a rapidly changing product like in the case of e.g. influenza vaccines. Another significant problem for the development of new phage therapies, also addressed in the paper, lies in the reluctance of pharmaceutical companies to invest into the field. The potential obstacles for more private involvement in phage therapy are many and range from considerable risks of failure, reputational damage, and unforeseeable side-effects to insufficient certainty with regard to intellectual property protection and guarantees of a profit.
Considering that AMR poses such an evident threat, it appears more important than ever that regulators across the globe develop proper approaches to phage therapy. Although phage therapy might never fully replace antibiotics, it might offer the best – or only available – therapy for patients in whom drug treatments have failed. Since the danger is imminent and there is reason to believe that phage therapies will often (arguably not always) be most efficiently developed in Private Public Partnerships (PPPs), this might also require decisions on how to best incentivize private investment into this promising, but risky field. Recent developments on both sides of the Atlantic attempting to enhance the developments of antibiotics, such as the US GAIN Act or the EU IMI initiative, as well as “delinkage models,” surely provide a good basis for further considerations.
Part II of this contribution will elaborate a little further on the IP situation in phage therapy and discuss alternatives to IP protection.