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.
Thanks for your encouragement - much appreciated!
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