FDA and Antibiotics - Its Coming!

As reported by Bloomberg, in a recent discussion with FDA advisors, Commissioner Hamburg noted that the FDA is considering a faster development pathway for drugs that address unmet clinical needs.  High on her list is antibiotics for infections that are not well addressed by our current antibiotic armamentarium. Such rapid development pathways would result in a label limiting the approval for use to circumstances in which the new drug is actually needed.  Dr. Hamburg discussed the risk-benefit calculation that would be required not only by FDA, but by us as a society.  In this regard, I think Dr. Hamburg is well behind the times.

Certainly physicians, especially those practicing in our hospitals and certainly those in our military hospitals, already understand the risk of not having adequate therapy for serious infections caused by pathogens resistant to all antibiotics or all but those that have never been demonstrated to work in the infections for which the physicians must use them. Physicians understand that the risk of emerging resistance even to these treatments is always there.

Carbapenem resistant Gram negative bacilli, including Acinetobacter, Klebsiella and other Enterobacteriaceae, and Pseudomonas already occur with relatively high frequency in large, academic medical centers throughout the US. The CDC demonstrated that in 2007 (already 5 years ago) 80,000 of the 2 million infections acquired by Americans in US hospitals every year are caused by resistant Gram negative pathogens and of these, an astonishing 63,000 cannot be treated with reliably effective antibiotics.  In some hospitals, 80% of Acinetobacter strains are resistant to all but those antibiotics that are toxic and may not work well. Almost all states have reported infections caused by carbapenem-resistant Klebsiella. Clearly these extensively resistant pathogens represent an ongoing risk to American patients in hospitals.

On the risk side we must add the increased risk of new treatments that are studied in smaller numbers of patients before they are allowed on the market. Here there may be an increased risk of side effects that are not detected during these smaller clinical studies. There may also be an increased risk of accepting a smaller data set supporting the idea that these new treatments actually work.  Both of these risks can be mitigated in two ways. First, continued study of the new therapies looking at both safety and efficacy would almost certainly be required in any case. Secondly, in order for companies to provide a return on their investment, the price for such therapies will be high (see the guest blog by Lew Barrett).  This will, by definition, limit the use of these therapies to patients who need them and thereby reduce the exposed population to those most likely to benefit.

The remaining question is how the FDA will implement this new pathway for antibiotics. This is a topic of ongoing discussions at the agency as noted by previous blogs. It is important that this be done soon since a number of products in the pipeline are seeking such a pathway so that they can get to patients quickly. Europe is well on their way to accomplishing this and they will be holding a workshop where this issue will be discussed the end of this month. The FDA needs to get on board quickly with a feasible pathway forward.  As I have stated before, a good starting point might be for the FDA to harmonize with Europe.