Thursday, January 26, 2017

The New Antibiotic Paradox

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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