"Superbugs Require Super Drugs: An Examination of Why Existing Incentive Programs Have Failed the Antibiotic Field" (Part 1 of 2)

Editor's Note: One of the great pleasures of running a site like Blawgconomics has been the opportunity it has afforded me to collaborate with incredibly talented guest contributors who often have interests and knowledge far outside my (self-proclaimed) areas of expertise.

Today provides a very special example of this as I have the honor to introduce not only the 200th posting to the site, but also Ms. Alissa Fideli's premiere as a contributor. Ms. Fideli is a fellow student at GW Law, and focuses primarily on intellectual property law. Her contribution below, 'Superbugs Require Super Drugs: An Examination of Why Existing Incentive Programs Have Failed the Antibiotic Field' is Part 1 of 2, and is adapted from a larger thesis of the same name.

Though the underpinning of Ms. Fideli's article is IP law, the economic considerations and implications of her analysis are tremendous. Though it is true that pharmaceutical companies exist to make a profit, it is also true that their products serve a public interest. Indeed, this is the foundation of the current drug patent regime in states such as the US; governments try to serve the public interest by ensuring R&D and production of drugs via the promise of monopoly profits for protected periods.

However, the world is ever-changing, and the realities of today are not being properly reflected in the current patent incentive regime. The things that make us sick are simply too short-lived and too effective at beating the drugs we have developed over the long-term to make exclusive, long-term patent protections an effective stimulus for R&D in many cases. In addition, the proliferation and ease of global trade and travel have perhaps lead to a point where global cooperation in IP laws for drugs has become necessary. Ms. Fideli addresses these problems below; Part 2 focuses on solutions.  

Introduction

Mariana Bridi da Costa was a 20-year-old Brazilian model who came to the hospital complaining of kidney stones in December of 2008. 1 Mariana was released from the hospital that day and returned four days later, exhibiting life-threatening hypotension; she was suffering from septic shock caused by a Pseudomonas aeruginosa infection in her urinary tract that had subsequently spread through her bloodstream. 2 Doctors did all they could to treat the young model; they administered intravenous antibiotics and also amputated her hands and feet and removed her kidneys in an attempt to stem the spread of the infection. 3 Unfortunately, their efforts failed and she died just days later. 4

The bacterium that infected Mariana was P. aeruginosa, a Gram-negative bacterial strain that has recently emerged as an important culprit in life-threatening nosocomial infections. 5 Much like methicillin-resistant Staphylocccus aureus (MRSA), which haunts hospitals as one of the most prominent and dangerous nosocomial infections, many Gram-negative and Gram-positive bacteria are becoming increasingly resistant to multiple antibiotics, making these infections nearly impossible to treat. Some estimates state that tens of thousands of hospital patients die annually from antibiotic resistant bacterial infections. 6 Gram-negative bacteria are particularly problematic because they are inherently more difficult to kill; they have an additional cell membrane that makes it more difficult for antibiotics to permeate the cell, and often produce enzymes that are capable of breaking down antibiotics when they do permeate the cell, or harbor pumps in their cell membrane that eject the antibiotics from the cell. 7 Pharmaceutical companies are not focusing their efforts on creating new antibiotics; there are currently no antibiotics in Phase II testing or beyond, and this is one of several factors that contribute to the lack of R&D investment in this field. 8

Various incentives exist to encourage R&D in rare diseases and other routinely neglected pharmaceutical areas, such as orphan drug and fast track designations, hatch Waxman exclusivities, and run-of-the-mill patent protection. All incentives provide some form of market exclusivity, which is typically the most valuable and most sought after incentive, and some provide tax credits or other monetary incentives. But regardless of the presence of incentives, pharmaceutical companies are still reducing their R&D in antibiotics and some are withdrawing from antimicrobial research completely. 9 This retreat is due to a combination of several factors.


Pharmaceutical companies weigh a number of considerations when deciding whether to begin investing in R&D for a particular drug, including the size of the patient population, how the product will fare against competition, the obtainable price for the product, and the investment required to bring the product to
market. 10 One of the factors weighing in favor of abandoning antibiotic research is that antibacterial products are expensive to develop because of stringency of clinical trials required. 11 In addition to the cost, the typical course of treatment for an antibiotic is short, generally only a week or two, and is therefore is less profitable than a drug that treats a chronic disease. 12 Furthermore, the entire process is frustrated by the fact that bacteria are able to mutate rapidly and quickly develop resistance to antibiotics. 13 The rapid rate at which bacteria develop resistance to drugs affects the possibility of future sales of a particular drug. 14 A drug that combats a particular strain of bacteria may only be effective for a short time, until the bacteria develop resistance; generally this period of time is far shorter than the life of a patent. This problem, in turn, leads to another for pharmaceutical companies: the best and newest drugs are being “saved” and used only when absolutely necessary. 15 The rapid development of resistance causes healthcare professionals to be more cautious about prescribing antibiotics, especially new, highly effective drugs that come on the market. 16

Pharmaceutical companies are businesses, and thus the costs weigh very heavily in this balance, therefore without the prospect of a lucrative return on a company’s investment, the company has little incentive to pursue research. 17 Unfortunately, this results in large pharmaceutical companies essentially neglecting antibiotics in favor of expending their efforts and funding toward finding the next blockbuster drug or at the very least antiretrovirals or drugs to treat chronic diseases. 18 The incentives that currently exist to encourage research have failed to spur pharmaceutical companies to invest in antibiotics; as such, it is clear that a new approach is necessary.


1. Kevin Pho, M.D., KevinMD.com, Her Hands and Feet Amputated, a Brazilian Model Dies from Pseudomonas aeruginosa Sepsis. What Happened?, http://www.kevinmd.com/blog/2009/01/her-hands-and-feet-amputated-brazilian.html (last visited Apr. 27, 2010).
2. Id.
3. CNN.com, Gram-negative Bacteria are Drug-resistant Superbugs to Watch Out for, http://www.cnn.com/2009/HEALTH/dailydose/02/20/gram.negative.bacteria/index.html (last visited Apr. 27, 2010).
4. Id.
5. Andrew Pollack, Rising Threat of Infections Unfazed by Antibiotics (Feb. 26, 2010), available at http://www.nytimes.com/2010/02/27/business/27germ.html.
6. Id.
7. Gram-negative Bacteria, http://www.horizonpress.com/gateway/gram-negative-bacteria.html (last visited Apr. 27, 2010).
8. CNN.com, Gram-negative Bacteria are Drug-resistant Superbugs to Watch Out for, http://www.cnn.com/2009/HEALTH/dailydose/02/20/gram.negative.bacteria/index.html (last visited Apr. 27, 2010).
9. Jeffrey L. Fox, The Business of Developing Antibacterials, 24 Nature Biotech. 1521 (2006).
10. David M. Shlaes, The Abandonment of Antibacterials: Why and Wherefore?, 3 Current Opinion in Pharmacology 470 (2003), available at http://antiinfectivesconsulting.com/PDF/Abandon.pdf, at *1.
11. Id.
12. Gary Taubes, The Bacteria Fight Back, 321 SCIENCE 356, at 359 (2008), available at http://www.sciencemag.org/.
13. Shlaes, supra note 10, at *2; Taubes, supra note 12, at 359.
14. S. Ragnar Norrby et al., Lack of Development of New Antimicrobial Drugs: a Potential Serious Threat to Public Health, 5 LANCET INFECTIOUS DISEASE 115, at 116 (2005).
15. Taubes, supra note 12, at 359.
16. Id.
17. Id.
18. See Fox, supra note 9, at 1521.