I just returned from giving a talk to microbiologists on the
issues surrounding the clinical development of antibiotics with activity
against specific pathogens – that is – the opposite of so-called broad-spectrum
drugs. I used as an example an antibiotic that targets Pseudomonas aeruginosa, Polyphor’s POL 7080.
Microbiologists play an important role in
constraining the use of antibiotics in both the hospital and community
settings. They are interested
in the development of antibiotics that are more specific and therefore less
likely to engender antibiotic resistance as collateral damage. What I mean is – when treating someone for a
Pseudomonas infection with a carbapenem antibiotic, you may select for resistance
in Klebsiella since the carbapenem kills indiscriminately. At least with a drug that targets only
Pseudomonas, you only have to worry about selecting resistance in Pseudomonas.
I pointed out that, at least today, from a regulatory
point of view, we still don’t know how to run a feasible trial that will
result in marketing approval for such a drug. While I am confident that this
problem will ultimately get solved, I am not so sure about the business model
for such a drug.
The problem for this sort of antibiotic is that it will be
used, at best, only sparingly. From the stewardship point of view – this is the
ideal situation. But, if the company marketing the product has to depend on
sales volume, it will be even more difficult to provide a return on investment
for this sort of antibiotic compared to a broad-spectrum agent that can more
easily be used on an empiric basis. Since companies are not in the business of
providing for the public health in some sort of charitable way, why would they
spend their limited resources on developing this sort of product? We, as a
society, need to provide a business model that will work.
In Europe, where most countries already have a form of
socialized medicine, the models
being discussed all include some sort of market entry reward. In all these
models, when a company gets approval to market an antibiotic that meets
pre-determined criteria, they receive a payment of some sort. How this payment is distributed is the basis
of the debate on which model to use. Regardless of the model, the payment would
be such that it would provide a return on investment for the company. While such a model was about to be put into use, I understand that everything is now on hold awaiting a better understanding of what Brexit will mean for payers in Europe.
Here in the US, the model that seems to be preferred by
people discussing this issue is the so-called patent voucher. In this system,
a company that successfully brings a needed antibiotic to market would be
rewarded with an additional period of exclusivity on the product of its choice
from its portfolio of marketed products.
If, for example, the company were Gilead, it might choose extra time of
exclusivity for one of its multi-billion dollar Hepatitis C drugs. This would
guarantee a return on investment for the new antibiotic even if it were only
used for a small number of patients every year. The last time this model was discussed by the
lobbying group from the Infectious Diseases Society back in 2004-5, the model
was dead on arrival in congress partly because of the blowback from both
consumers and the generics industry. How
this model will fare under a Trump administration is impossible to predict –
but past experience on the Hill is not encouraging.
My own opinion is that we need something beyond price and
that Allergan’s experience makes a strong argument for that view. Allergan will
now struggle for several years to achieve the analysts’ peak annual sales
forecast of $300 million if it ever does so. And this level of sales, albeit it
is only in North America, may not be enough for many companies in any case. Other
pharmaceutical companies will be watching this closely and they may not be
encouraged. But we need more large
companies to join the fight against antimicrobial resistance through the
research and development of new antibiotics active against resistant pathogens.
The experience of Allergan coupled with continued dithering on the Hill does
not bode well for our goal of bringing more large companies into the field.
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