Tuesday, August 28, 2012

Antibiotics in the News

The NIH recently reported  an outbreak at the NIH hospitals where 11 patients died with infection caused by a KPC carbapenemase producing Klebsiella resistant to virtually all antibiotics.  The outbreak was finally uncovered by DNA sequencing of all Klebsiella strains isolated either as part of the infection or from patients who were just carriers.  This was an enormous effort but it did allow physicians and epidemiologists at the hospital to track the infection to help stem its spread. The story was picked up by several news outlets after its publication last week. This in turn led to the inevitable question – where are the new antibiotics we need to treat these infections? 

This last question led to several subsequent reports including one from the Washington Post and a segment of the Diane Rehm show on NPR public radio. While most of the time on the Diane Rehm show was dedicated to understanding the outbreak, there was a brief segment on exploring where the new antibiotics are or are not. I was interviewed along with Ed Cox.  I tried to make points around the difficulties with discovering new antibiotics, with the marketplace, with industry consolidation and with companies just dropping out of antibiotic R&D altogether.  But I only got to 2-3 of these.  Ed pointed out how the FDA is looking at accelerated and higher risk pathways for new products for these very resistant infections.  I know that Ed also understands that we have to have feasible pathways for traditional development as well – but he didn’t get a chance to go there either.

At the same time, a Financial Times article highlighted how many pharmaceutical companies are negotiating their trial designs for registration of antibiotics for the market in Europe putting the FDA in second place. This emphasizes the risk that the US is running. If trial designs are negotiated in Europe where the development pathway for antibiotics remains reasonable and feasible (see my last blog on this), the US will be left in a take it or leave it position when these trials are completed.  None of us want to be in that position.  This is such a turnaround from the 1990s when EU was the conservative and more difficult regulatory agency and the FDA was more approachable and tried to make sure trials were feasible. But EU never got to the point where the FDA is now – requiring infeasible trials with endpoints that many physicians believe are clinically irrelevant and that I think are unnecessary. 

Hopefully the FDA will act quickly to provide feasible and reasonable trial design paradigms for antibiotic approval here in the US.  The fastest way for the FDA to accomplish this would be to rescind all previous guidance (again) and to harmonize with EU.  Then they can slowly evolve away from that position if needed.  But this strategy would give the industry, patients and physicians an immediate pathway forward that would be global.  What is wrong with that idea?  Why can’t we just do that?  I hope to ask that question at the Brookings Institution in a couple of days. 

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