New drug development: the case of antibiotics

I was going to wait to discuss recommendations for encouraging new drug development that better matches public health needs until I had provided more background. It's complicated, and it depends on the specific issue. But let me take the example of antibiotics. 

 

This is an urgent global problem. As most people know, microbes continually evolve and they will evolve to become resistant to commonly used antibiotics. This article in Clinical Infectious Diseases explains the problem and also why drug companies are not doing enough to develop new classes of antibotics.

Antimicrobial resistance is a profound global health threat of the 21st century. The United Kingdom’s AMR Review estimates that by 2050 as many as 10 million persons a year will die of drug-resistant infections if solutions are not found [1]. The World Bank projects that, without containment of antimicrobial resistance, annual global gross domestic product will decrease by 1%, that is, >$1 trillion annually from 2030, and the hardest hit will be persons in low-income countries [2].

Although resistance levels are increasing globally, the world currently lacks the drug candidates to ensure a diverse and robust pipeline of antibacterial drugs to withstand technical attrition and increasing drug resistance [3, 4]. As of December 2016, there were only 38 candidates in the antibacterial clinical development pipeline [5]. Most of these products will not reach the market, and only a handful of candidates are expected to have activity against urgent threat pathogens. The World Health Organization has identified a list of 12 pathogens that represent the global public health need for new antibiotics [6]. Without new antibiotics targeting these pathogens, mortality rates for untreatable infections are expected to increase. This would represent a step backward in modern medicine, not only for the treatment of infections but also for the ability to perform standard surgeries and cancer chemotherapy, areas that require effective antibiotics as prophylaxis [7].

The lack of antibacterial drug candidates is a function of both the scientific challenges of antibacterial drug development and the lack of profitability that currently exists in the antibiotic market, particularly when compared with other therapeutic areas. Antibacterial drug development is hampered by the conventional pharmaceutical business model, in which revenues are based on volume sales. Antibiotics are unique in that the more that they are used, the faster resistance develops [8]. Therefore, society should actually value and reward access to new antibiotics against specified unmet public health needs, not sales volumes.

As further background, the main incentive for new drug development is basically the same as the incentive for all technological innovation, the patent system. In the case of pharmaceuticals it's a bit more complicated because companies apply for a 20-year patent when they discover a drug candidate, but it typically requires 7 years or more of clinical trials before they can get FDA approval to actually sell it. So they can get additional exclusive rights from the FDA. Typically, market exclusivity lasts for 12 to 14 years.  But, this doesn't suffice to incentivize new antibiotics. If you read the CID article, you will read that the Generating Antibiotic Incentives Now (GAIN) Act provides 5 additional years of exclusivity for new antibiotics. While five antibiotics have received this benefit, none has a novel mode of action, in other words they don't do anything to address the problem of drug resistance. As the article says:

Without an attractive market for antibiotics, private sector investment will continue to decrease. The number of large pharmaceutical companies that invest in antibacterial R&D has decreased significantly in the last 3 decades, to only about 5 companies today [17].

The point is that ordinary market incentives don't work to serve the public interest. The article discusses various ways that incentives can be adjusted. I don't want to get into the weeds of that, I just want to make the point that governments need to manage incentives. The most straightforward way to do that is to invest directly in antibiotic development. This could be done through agreements with pharmaceutical companies that will allow them to sell the resulting product, but at a pre-specified price that allows them only a reasonable profit for manufacturing it, and doesn't enable them to profit from co-opting the public investment; and also allows them to gradually repay the government for its investment. 

 

Yeah I know. Soshulism.  

Basic literacy: The entire point of this post, and the carefully sourced and well-reasoned scholarly article on which I base it, is that marketing exclusivity does not result in the necessary development of new antibiotics. That is literally the exact conclusion this essay arrives at. Also, almost all basic biomedical research in the United States is funded by the federal government, mostly through the National Institutes of Health, which is largely responsible for the extraordinary revolution in medical science and therapeutics in the past 100 years. Yabbut that's socialism.