Saturday, June 26, 2010


Its been two years since the FDA has been struggling to provide guidance for sponsors trying to study pneumonia and skin and soft tissue infections.  In the meantime, the antibiotic approval drought at the FDA continues unabated as resistance fails to take a vacation.  So what’s going on in Europe?  Good question. 

The European regulatory authority, the EMEA, has stated categorically that the development of new antibiotics is its highest priority. This stands in stark contrast to the attitude at the FDA where standards based on 80 year old placebo controlled trials seem much more important than developing new antibiotics. I recently learned that the EMEA has not been following events at the FDA too carefully.  They are comfortable with their current position on pneumonia and skin infections as far as I can tell. As it stands now, Europe has no plans to provide guidance to sponsors on specific infections – they never have.  Europe has always been more flexible than the FDA but at the same time, less predictable and more variable in terms of both regulatory requirements for approval and ultimately for pricing within the individual markets of Europe. They have also been more difficult to deal with in that to discuss a topic with Europe, you must request Scientific Advice.  This meeting requires a set of advisors and takes several months to organize.  It has been much easier and more straightforward to communicate with the FDA.  Europe, on the other hand, has traditionally kept its word once advice is given whereas the FDA has been unabashed about changing its mind in the midst or even at the end of expensive Ph. III trials.

I have encouraged clients to approach individual European country agencies (e.g. MHRA in the UK or AFFSAPS in France) rather than Europe (EMEA).   Meetings are easier to arrange – but of course, the advice you receive may be different than what one might hear from the EMEA representing Europe.

Another problem in Europe is that even if you succeed in obtaining regulatory approval for your drug, you still have to negotiate the conditions of marketing and pricing with individual countries.  This adds to the delay in marketing in Europe and increases the uncertainty for companies.

So, with this in mind, how will Europe (EMEA/CHMP) deal with the recent FDA stance (or lack thereof) on pivotal trials in antibiotics?  Judging by past behavior, Europe will stick to its plan of not providing specific guidance for specific indications, but will be open to trials where the endpoints are as the FDA has specified.  Since, in the case of SSSI, there is a clear correlation between success at the early timepoint and success at the customary later timepoint, The EMEA will probably be happy with either.  The EMEA also understands that there are limits to what sponsors can do to run pivotal trials on a global scale – so they are unlikely to make sponsors use an endpoint in Europe that markedly differs from that required in the US. 

I would guess that the same arguments would hold when the FDA finally issues guidance on CABP.  The major issue there will be around trial feasibility.  In the case of CABP, my guess is that the EMEA remains happy with the old endpoints and that if the trials required by the FDA are infeasible, the EMEA will stick with its current approach.  This would theoretically allow registration of antibiotics for treatment of pneumonia in Europe that would not be acceptable to the FDA. 

Apparently, the CHMP will address at least some of this in a meeting this Fall.  Maybe, by then, we will have some idea of where the FDA will be going for trials in pneumonia.

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