For the past decade or more the Wellcome Trust, BARDA and
others have been funding antibiotic research at various levels from early
discovery through preclinical and clinical development. Some of these projects
have poor commercial potential. This is
clear from the products that are highly specific for only one species such as Pseudomonas aeruginosa or Acinetobacter baumannii with the latter
being even more commercially challenging than the former.
Projects like this might include antibody therapies (used
for therapy rather than prophylaxis), virulence inhibitors such as those that
might target the type III secretion system or quorum sensing mechanisms or directly acting antibacterial small molecules such as Polyphor's POL7080.
All of these are high risk since none of these approaches have resulted in a
marketed antibacterial product. In general, such projects are undertaken in
academic labs or by biotech companies and start-ups. As projects advance, they
become more expensive. They ultimately require investors to put down 10s of
millions of dollars. These investors
know that putting up even more money to support pivotal clinical trials will be
even more difficult. They almost always want to have the prospect for
acquisition by or at the very least partnering with large pharma. But given the
commercial potential for these highly specific approaches, large pharma will
balk.
At the same time, such products apply less pressure to the
microbiome simply by virtue of their specificity – the very property that
decreases their commercial potential. They are less likely to select for resistance
at least among organisms other than those specifically targeted. This is a good
thing. This selectivity leads, by
definition, to good stewardship. We all want to see better antibiotic
stewardship both in the hospital and in our communities.
Of course, we all shout, small companies don’t need to make the same profits that large pharma needs. $100 million in peak year sales might be enough for biotech especially if the bulk of the development costs comes from non-dilutive funding from the Wellcome or BARDA. But will they even make that much? The recent
experience with Avicaz in the US market gives everyone pause.
We can readily see the paradox for these putative new
research efforts even if they could ever result in a useful product. The characteristic
for which they are being sought, specificity, is the very one that will lead to
their commercial demise.
The resolution to the paradox is simple. Money. We need a
new business model for antibiotics. Many
have been discussed
in my blog and most recently in an editorial
in the New York Times. Entities like BARDA and Wellcome will have an
increasingly difficult time funding research into new antibacterial strategies
that provide for good stewardship but where putative products are also
commercially questionable unless we can find a way to provide some sort of
commercial path. These could even include government purchases such as those
that have already been carried out for potential pandemics or for biothreat
agents. For this, though, we need funding.
And, as I noted
previously, we certainly need it here in the US.
My own belief is that without a commercial solution, our
government and private investments in antibacterial research and development will, of necessity, disappear
for lack of success in bringing products to market. No one wants us going in
that direction. Speaking for us aging boomers – the sooner we fix this the
better!
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