Thursday, October 22, 2015
The Antimicrobial Resistance Congress - Meeting Notes
There were several key presentations from various funding agencies including BARDA, NIH, IMI and the Wellcome Trust. With the exception of the Trust, it was abundantly clear to everyone that without additional funding, the efforts of these agencies to go beyond their current funding levels or even to maintain them will be threatened. The funding from these agencies goes to everything from early discovery all the way through phase III clinical development and has been very important for academia and both small and large pharma in the pursuit of new antibiotics. Any diminution or even an inability to expand these efforts would be a terrible tragedy.
Several non-antibiotic approaches were discussed including antibodies, peptides and virulence. Some are being examined for prevention while others are thought of as adjunctive therapy. All of these approaches will mean superiority trials. How to set control levels of response within these trials then became a topic of conversation. More later.
Diagnostics, both rapid and not, were discussed by FDA. On the more usual antimicrobial susceptibility testing devices, it is clear that the delays in availability of these devices after antibiotic launch is not being well addressed by FDA. Until this occurs, the delays will continue to impede acceptance of new antibiotics by end users – not a good state of affairs with continuing increases in resistant infections.This will require some sort of preliminary breakpoint from FDA that would allow device manufacturers to begin their process prior to approval. Everyone will have to work at risk. Will this ever occur???
Stava Epstein gave a wonderful and elegant talk on the iCHIP. There was nothing really new in his talk, but it was exciting to hear him speak about this wonderful new technology that may revolutionize the way we look for new drugs.
Dr. Sumathi Nambiar provided a discussion on the QDIP designation and on market authorization for products to treat resistant infections. In the latter portion of her talk, she admitted that the FDA remains somewhat lost on how to proceed in pathogen specific trials. She noted that the FDA prefers a hybrid approach with non-inferiority trials plus some additional data on activity against resistant infections.
Later, Dr. Nambiar was roped (my fault) into a panel discussion where the topic of an orphan drug designation for such unmet needs antibiotics was raised. As I discussed in a previous blog, the orphan drugs group is still back in the 1990s of antibiotic development. They only think in terms of broad clinical indications like urinary tract infection, pneumonia, etc. In this thinking, the affected populations are much too large to be considered for orphan drug status (200,000 individuals or less in the US). But a pathogen specific indication where the drug is indicated only for those with few or no alternatives (4500-7500 per year in the US for carbapenem-resistant Enterobacteriaceae for example) has not been considered even though this is addressed by the unmet needs guidance both in the EU and in the US. As a result of this discussion, Dr Nambiar agreed to raise this issue with her FDA colleagues. We await, once again, further developments.
Finally, the economics of the antibiotic markets was broached by Kevin Outterson and Barrett Thornhill. The proposals for so-called de-linking, where there would be an attempt by governments to provide a guaranteed return on investment for companies pursuing antibiotics for resistant pathogens seem to be in limbo in the US since we have no congress. In Europe there is hope that such an approach will bear fruit – but whether that will occur soon or with the usual tectonic EU speed is hard to predict. The precise method of implementation of such payments also remains nebulous. These discussions reminded everyone that, at the end of the day, to progress, we need money. And, especially in the US congress, that remains a dirty word.