Tuesday, November 9, 2010

Antibiotics and Incentives

A recent article by Andrew Pollack in the New York Times discussed the idea of incentives for the pharmaceutical industry to encourage them to develop new antibiotics. Mr. Pollack points out that while antibiotic resistance is rising, the antibiotic pipeline remains dismal with only two new antibiotics approved by the FDA in the last two years. On a more optimistic note, he also shows data from the FDA that the number of antibiotics in clinical trials has soared since 2003.  Some of these trials are being carried out by large pharmaceutical companies and will likely lead to marketed new drugs.  These include ceftazidime + NXL-104 and ceftaroline-NXL104 trials now being driven by Astra-Zeneca and Forest/Cerexa and Calixa-tazobactam from Cubist (a mid-sized company).  Unfortunately, many of the trials cited by the FDA data are early stage trials being funded by privately held, venture-capital-based biotechs.  These small companies will, probably, be unable to afford the phase III trials that will be required to register a new antibiotic.  They will therefore be dependent on one of two sources of funding; (1) the public markets or (2) large pharmaceutical companies.  But the public markets are virtually non-existent at least for now.  Trius’ public offering resulted in a vastly lowered share price compared to what the company had envisioned.  It is still not clear to me how they will actually pay for the two phase III trials required to register their drug, torezolid. Large pharmaceutical companies that are still interested in antibiotics is a rapidly disappearing species with only 5 of the 13 largest companies in the US and Europe still in the business of discovering antibiotics.  And when companies abandon the field, they lose their expertise.  They become unable to appropriately evaluate new opportunities.  This leads them either to make poor decisions or simply leads them away from in-licensing antibiotics. 

The Infectious Diseases Society of America has proposed a number of incentives for industry.  They also strongly support enactment of The STAAR Act (STRATEGIES TO ADDRESS ANTIMICROBIAL RESISTANCE ACT).  The STAAR Act, while an important step forward, does not really address key incentives to the industry for the development of new antibiotics active against resistant pathogens. Incentives supported by the IDSA do not really include those most likely to work, in my opinion.  The incentives that I think are most likely to work include (1) the wild card patent exclusivity, (2) the push-pull mechanism from the London School of Economics report and, perhaps most importantly, (3) a feasible path forward for new antibiotic development from the FDA and EMEA.  Although the latter might not be formally considered an “incentive”, we will have no antibiotics without it.  The wild card patent exclusivity would allow a company like Pfizer to obtain an additional 6 months to two years of patent exclusivity for a drug like Lipitor in return for marketing a new antibiotic active against resistant pathogens.  This has been shown by Spellberg and coworkers  to be cost effective given the societal costs of antibiotic-resistant infections.  The push-pull mechanism would provide support for development, say for the phase III trials required for registration, plus a guaranteed initial government purchase of a new antibiotic for resistant infections.  This would reduce the company’s risk and at the same time provide an initial sales spurt that would more than offset launch costs and provide an immediate return on investment for the company.  In my view, this is superior to the wild card option in that the costs to taxpayers would be less, but the incentive would still work quite well.

But all this remains a dream. So far, no one except me and the IDSA, supports giving money to pharmaceutical companies and we still do not have the kind of regulatory path forward that we need to even consider developing needed new antibiotics.  Somewhere, over the rainbow . . . 

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