Once again I was privileged to be a participant in an ongoing conversation on antibiotic development and the FDA involving experts from large and small pharma, academia and the Infectious Diseases Society of America. The conversation started with the ironies of FDA statements and their recent draft guidance documents, especially that focused on the development of antibiotics for skin infections. I will leave that part of the discussion for a future blog. But the conversation ultimately found its way to the topic of what can be done to ameliorate the situation. This, after all, is the ultimate conundrum. We, for various reasons, believe that people will, at the end of the day, be reasonable and rational. We are always disappointed and surprised when that is not the case. But anyone who has been living the nightmare of the FDA and antibiotic development over the last decade will understand what I am talking about. We live in a world where reason and rationale have given way to survival in a hostile political environment.
So – what to do? I think it is too much to hope that the FDA will come back to some semblance of feasible trial designs with realistic and clinically relevant endpoints for antibiotics in the near future. I also think that legislation to provide real incentives for industry and real limits for the FDA is beyond reach this year. I continue to believe, though, that the way forward lies overseas.
Americans must be made to realize what the FDA and congress are doing to them as far as antibiotics are concerned. First, the continued use of antibiotics in animal feed is only going to continue to increase the incidence of resistant infections in our citizens. If Montana has its way that will be our fate. Now that we will continue to assure ongoing resistance, we will also assure that we have no new antibiotics to fight these infections. The FDA has constructed a series of guidances for industry that require either infeasible trials or use clinically irrelevant endpoints or both. So even if industry wanted to develop new antibiotics, and most large companies have already voted with their feet and abandoned the area, they can’t – at least not in the US. One of the few exceptions is in skin infections where the trial designs are at least feasible, but where the endpoint is at best of debatable clinical relevance. The other issue for companies is that the trial designs for skin infections required in the US have nothing to do with those required in the rest of the world – this creates additional (but not insurmountable) challenges for industry.
Where is congress in all this? They are busy trying to protect cattlemen in Montana by allowing continued and unnecessary use of antibiotics in animal feed. They are unable to pass legislation to provide for real incentives for companies to develop antibiotics where the return on investment for companies is poor. And, congress is unable to rein in an FDA gone mad. Trying to speak to congress about this is a little like swimming upstream in jello. While the basic concept of the problem we face is easily understandable, coming up with legislation to address the problem is not so easy. The GAIN act, for example, is going to be too little to really incentivize companies and too weak to effect change at the FDA. But even that bill is having trouble making it through congress. A plan with real teeth has been proposed by the London School of Economics and has been proposed as law to the European Commission. This plan would work – but has not even made it into any sort of bill in the US congress. All we have is a US-EU Task Force that will make recommendations someday.
In addition to continuing to speak with congress and the FDA, I think the way forward is to actually develop new antibiotics active against resistant strains in the rest of the world. Companies should negotiate reasonable trial designs in Europe and then present these to the FDA. If the FDA makes it impossible to carry out the trials – so be it. These new products will at least be available in other areas of the world where the medical need is great. Companies can always re-approach the FDA at the time of submission for marketing approval in Europe or even post-approval. I know that this advice will be hard for large companies to swallow since the US market, even though stagnating or shrinking, is still large and therefore hard to give up. Nevertheless, for those truly committed to the development of antibiotics, providing them for the rest of the world is still a very good thing. And putting pressure on FDA and congress to make approval of new antibiotics to fight resistant infections feasible in the US is also better than not developing antibiotics at all.
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