Fecal Microbiota Transplantation (FMT) may emerge as a serious alternative to antibiotic therapy. Phage therapy has not, despite many more decades of research and clinical experience. It's not as though the potential of phage therapy is a secret - there are any number of editorials and reviews that propose we give phage therapy "another look", as we combat increasing rates of antibiotic resistance. Yet there are only 4 phage therapy trials listed on ClinicalTrials.gov, and one of these appears to never have gotten started. By contrast, 18 are listed for FMT therapy, a number that is surely an undercount given how recently the FDA began insisting on formal trial protocols.
Phage therapy has been around for many decades, predating the antibiotic era, and continuing in use in Eastern Europe. Although only one placebo-controlled clinical trial has been reported, it gave encouraging results for treatment of otitis media due to Pseudomonas infection. But those results were published in 2009. The sponsor, BioControl (now AmpliPhi Biosciences) no longer features the otitis project on the company's website, although there is a respiratory Pseudomonas project in preclinical development.
I would suggest that phage therapy has an insuperable intellectual property problem. Phage aren't like other drugs. It's not just that they are alive (or biological, if you prefer), it's they are too easy to make and too hard to define.
Phage experiments are really easy to do. When physicists with no lab skills decided to "solve" biology in the mid 20th century, they turned to phage as model systems. Phage are everywhere in the biosphere, they multiply by many orders of magnitude in a few hours, and they are conveniently stored in the fridge when it's time to call it a day in the lab. Because they are so prolific and so easy to handle it's easy to select phage that have desirable properties, such as enhanced killing of pathogenic bacteria.
You can obtain patents on these phage, but it won't protect your company from completion. We never filed on our proprietary phage at MicroPhage, because it would just be too easy for someone else to independently select phage that were functionally equivalent yet compositionally different, and so did not infringe.
This is why no pharma company or other deep-pocketed entity has ever put serious money into phage therapy. Imagine that you developed a phage cocktail that suppressed wound infection. There's little to stop a second (or third, or fourth etc) group from doing the same thing, as the concept of phage therapy of wounds is in the public domain. It would be essentially impossible to show that one formulation was superior to another in clinical trials. That would leave your company to compete on cost, driving everyone's margins down to nothing. Generics compete on cost, but the makers of generics don't have to spend hundreds of millions of dollars to perform clinical trials before they see a cent of revenue. No one is going to put up the money for high-risk clinical trials whose best outcome is a product with a small addressable market and low margins.
This is a failure of our profit-driven system (to be clear, I have enthusiastically participated in and profited from this system). There is no doubt that patients would benefit from phage therapy. It is becoming increasingly clear that patients are benefitting from FMT. A key question for the future of FMT is whether it can avoid the same IP trap as phage therapy. I don't think so. Like phage cocktails, I expect that FMT cocktails can be diverse in composition, yet functionally equivalent. There are dozens, if not hundreds of bacterial species to choose from in making a defined FMT cocktail, and an unlimited number of strains within species. It is telling that of the 18 FMT trials listed on ClinicalTrials.gov, not one is sponsored by a commercial entity.
Thus there is a serious chance that FMT will end up like PT - a marginal or experimental therapy practiced by a few experts. The only way forward that I see is for a not-for-profit (perhaps crowd sourced?) entity to pick up the costs of developing a manufacturable formulation and putting it through clinical trials. The standard model of venture or pharma financing is just not going to work.
Posted with Blogsy
No comments:
Post a Comment