When Antibiotics Fail

The following opinion piece, authored by Pew’s senior director of health programs Allan Coukell, was published in The Hill’s “Congress Blog.” The commentary advocates for the creation of a unique approval pathway for limited-population antibacterial drugs.

In August 2004, 20-year-old Marine Lance Cpl. Jonathan Gadsden was seriously wounded by a roadside bomb in Iraq. He made it all the way back to a military hospital in Maryland and by September seemed on the path to recovery. Then signs of infection appeared. His doctors gave him powerful antibiotics, but to no avail. He died a month later.  

Gadsden was one of an increasing number of Americans who have contracted deadly, drug-resistant bacterial infections that no available antibiotic can treat. He and his doctors simply ran out of options.   

Unfortunately, the threat of antibiotic resistance has only intensified in the years since Gadsden’s death. Over the past decade, the world’s leading health authorities, including the World Health Organization and the U.S. Centers for Disease Control and Prevention, have identified antibiotic resistance as a serious global health threat. Yet the number of new antibiotics being developed is dwindling.

Although 29 new antibiotics were approved in the 1980s and 23 in the 1990s, only nine were approved from 2000 through 2010. Additionally, almost all the antibiotics that have reached the market in the past three decades have simply been modifications of earlier medications rather than novel products that can successfully treat the growing number of drug-resistant infections.  

Antibiotics are the foundation of much of modern medicine, so this lack of innovation puts us all at risk. Everyone from an immuno-compromised cancer patient to a person getting a root canal is in danger of acquiring an infection for which there is no viable treatment.  

Winning the fight against drug-resistant superbugs will require new antibiotics and a new regulatory path that addresses the unique challenges of bringing them to market. Congress is considering a streamlined drug-approval process that will make this possible.

The limited-population antibacterial drug, or LPAD, pathway would allow the Food and Drug Administration to review and approve new antibiotics specifically for patients with serious and life-threatening bacterial infections that are highly resistant to current treatments. This targeted approach would make antibiotic development more feasible by allowing for smaller clinical trials and enabling the FDA to focus on data specific to the limited, high-risk populations for which these new antibiotics will be used, rather than a more general population.  

As Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, recently emphasized, antibiotics approved using this new pathway would have to demonstrate the same substantial evidence of safety and effectiveness required of all FDA-approved drugs using a wide range of data, including human clinical trials. However, the focus on resistant infection will let the FDA make a risk-benefit assessment tailored to patients most in need.

In addition, these drugs would carry safeguards to ensure that they are used as intended, including:

• Prominent, mandatory branding so that prescribing physicians understand that the drugs were demonstrated to be safe and effective in limited populations and are intended for use only in those populations.
• Preapproval of marketing materials so that the FDA can review the materials to ensure that they reflect appropriate use of the drugs.
• Post-market surveillance by the Department of Health and Human Services to ensure that the drugs are used only for patients with unmet medical needs.  

Support for this pathway is broad, bipartisan, and growing. The House of Representatives has approved LPAD legislation, and Sens. Orrin Hatch (R-Utah) and Michael Bennet (D-Colo.) have introduced a companion bill in the Senate. The president’s 2016 budget calls for implementation of the LPAD pathway to help drive research and develop new drugs. And FDA officials have testified before the House that the pathway would enhance the agency’s ability to bring critical new medicines to patients.

As Dr. Margaret Hamburg, a former FDA commissioner, said in June: “This pathway … is an attempt to fine-tune the difficult challenge that FDA grapples with every day of balancing risks and benefits in order to provide the best possible treatment to patients. … This is an effort to reflect the realities of expanded disease that is burdening patients today.” 

The rise in untreatable bacterial infections is one of our most urgent public health problems, and has the potential to become rapidly worse as new drug-resistant pathogens emerge. We cannot wait until we have a widespread outbreak. The time to research and develop new antibiotics is now. 

Although no single policy can address all of the complex challenges of antibiotic resistance, the LPAD pathway is a critical part of the solution, and Congress should make it a reality.

Coukell directs health programs at The Pew Charitable Trusts.