New antibiotics are needed because bugs always win
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This week, the United Nations General Assembly, in an historic session, convened to address the global threat of antimicrobial resistance. UN Secretary General, Ban Ki-moon, described antimicrobial resistance as a fundamental threat to global health and safety. Indeed, the risks are real and profound. This year alone, there will be more than 700,000 deaths from infectious diseases. And as current antibiotics lose their ability to combat increasingly resistant pathogens, the World Health Organization projects that by 2050, as many as 10 million people could die annually as a direct result of antimicrobial resistance.

Bacteria surround and inhabit us. They are among the oldest form of life on earth, and for millennia, they have been adapting and evolving for one purpose: to ensure their own survival. Many bacteria are beneficial — even essential — to the survival of humans and other mammalian species. But certain bacteria pose risks to human health. In fact, through the course of history, bacterial infections have resulted in the deaths of more humans than any other cause.

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The introduction of novel antibiotics, such as penicillins and tetracyclines, completely transformed the treatment of infectious disease. Where death had been a near certain outcome, survival became the expectation. However, bacteria rapidly developed resistance to the early antibiotics. At the time, there was little concern, as the pharmaceutical industry was able to address resistance by developing new, more powerful antibiotics. Today, that is no longer the case.

During the first 10 to 15 years of this decade a number of factors affecting antibiotics — including regulatory changes in the statistical criteria and efficacy endpoint used to evaluate studies — resulted in a shift to longer development cycle times, more expensive trials, and greater regulatory uncertainty. The direct result was the pharmaceutical industry, for the most part pivoted away from developing new antibiotics due to the development risks and costs.   

At the same time, due to the lack of new antibiotics being developed, the use of generic antibiotics became ubiquitous. This further contributed to the increase in antimicrobial resistance. Without new antibiotics to treat resistant bacteria, the continued use of ineffective generic antibiotics further augmented the rate of bacterial resistance development.  

The convergence of all of these factors presents the recipe for the current threat we are now facing. In fact, the number of deaths in the United States from bacterial infections is again rising, as available antibiotics are losing the ability to treat them.

We are, right now, at serious risk of returning to a pre-antibiotic era.

The situation is dire, but not intractable.

Starting at the beginning of the 20th century, modern healthcare combined with sensible public policies — was able to markedly reduce the death rate from infectious diseases. Better sanitation and clean water supplies reduced the rate of bacterial infection, while improved medical and treatment protocols reduced the spread of infection and improved treatment outcomes.

Today, the same combination of smarter medical decision-making and responsible policies are needed, and the meeting at the UN is an important step forward.

The UN member countries, along with a coalition of Non-Governmental Organizations and the pharmaceutical industry, have pledged to take a number of steps to ensure the appropriate use of antibiotics. 

These include the reduction and eventual elimination of the use of antibiotics in animal feed and the implementation of policies to encourage the appropriate use of antibiotics to treat infectious disease — and, importantly, to prevent their use in the treatment of nonbacterial infections. The pharmaceutical industry has also committed to protecting water supplies from runoff from antibiotic manufacturing facilities.

These efforts are critical, but alone, they will not be nearly enough. The truth is, bugs always win. To keep pace, we will need to develop new antibiotics to fight them. And, to do that, we need public policies that encourage investment and innovation.

The passage of the Generating Antibiotics Incentives Now (GAIN) Act in 2012 and the FDA’s implementation of that law’s qualified infectious disease product (QIDP) provision, along with the Agency’s recent efforts to clarify guidance on clinical trial design have been significant steps in the right direction.

By establishing incentives for the development of qualified infectious disease products, a number of new antibiotics are — or will soon be — available to physicians.

But, in order to keep pace with the need, more incentives are required to induce novel antibiotic research and development. Sensible legislation has been proposed, including S. 185, the Promise for Antibiotics and Therapeutics for Health Act (PATH) Act and H.R. 512, the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) Act.

PATH is a regulatory incentive which would enable prompt approval of new antibiotics based on more limited populations studied — qualifying products would only be those intended to treat unmet medical needs for which there are no current options for patients.

DISARM would provide financial incentives under Medicare reimbursement, giving enhanced reimbursement to novel antibiotics addressing serious, life-threatening infections.

PATH had overwhelming bipartisan support at the committee level, and has been included as a part of the Senate's Innovations for Healthier Americans legislative package.

Policy engines also recognize the importance of incentives. The Margolis Center for Health Policy at Duke University has held multiple stakeholder meetings to identify further policy levels that can be used to increase investments in antibiotic research, including models breaking the traditional link between sales and volume.

Other countries are moving forward with such policies. The EU, for example, has advanced the DRIVE-AB initiative to encourage re-investment in antibiotics development and responsible use.

We cannot wait any longer. Congress should make the passage of legislation that facilitates and encourages the development of new antibiotics among its highest priorities. The threat is real and unavoidable. New antibiotics are among our most urgent medical need — we cannot forget that antibiotics, although used for limited treatment periods, actually are life-saving therapies.

Evan Loh, M.D., is the President and Chief Medical Officer of Paratek Pharmaceuticals


 

The views expressed by contributors are their own and not the views of The Hill.