As Congress prepares to return to work today, some of the nation's leading health organizations are urging lawmakers to pass legislation that could make it easier to get federal approval of new antibiotics for tough-to-treat infections.
The legislation, known as the Promise for Antibiotics and Therapeutics for Health (PATH) Act, would establish a new "limited population antibacterial drug approval pathway" for antibiotics that treat serious or life-threatening infections for which there are few or no other options.
The bill is part of the broader 21st Century Cures Act, a collection of 19 bills that would make changes to how the Food and Drug Administration (FDA) approves new drugs and medical devices. The House of the Representatives passed the 21st Century Cures Act in 2015.
"The new pathway proposed by PATH is necessary to develop novel antibiotics and bring them to the patients that need them most," the organizations wrote in a letter sent today to Senate leaders and the ranking members of the Senate Committee on Health, Education, Labor, and Pensions, which is reviewing the legislation. The letter was signed by 42 health organizations, including the Infectious Diseases Society of America (IDSA), the Alliance for the Prudent Use of Antibiotics, and the American Academy of Pediatrics.
The groups said the PATH Act could help stimulate the discovery and development of new antibiotics, which they see as one element in the multi-pronged approach to combatting the growing threat of antibiotic resistance. They noted that it's been more than 30 years since a new class of antibiotic was discovered and developed—a period that's also seen a sharp rise in drug-resistant bacteria.
"The proliferation of antibiotic-resistant bacteria—a result of decades of overuse combined with a lack of new drug development and innovation—threatens to bring us to a 'post-antibiotic' world in which even the most simple surgical procedure could have deadly consequences," the letter warns.
The groups said the legislation would be a regulatory complement to the 2012 Generating Antibiotics Incentives Now (GAIN) Act, which aimed to address the economic challenges of antibiotic development by giving drug makers additional exclusivity for antibiotics to treat serious and life-threatening infections.
Bill would allow for smaller clinical trials
According to Helen Boucher, MD, an infectious disease expert at Tufts University School of Medicine and a member of IDSA's Antimicrobial Resistance Committee, the PATH Act would help spur antibiotic development by enabling the study of antibiotics through smaller clinical trials than would ordinarily be required by the FDA, while including safeguards to ensure that the new drugs are safe, effective, and used appropriately. The new antibiotics would be specifically for patients with serious multidrug-resistant bacterial infections and would bear labels indicating the limited populations for which they are appropriate.
"In particular, we're talking about patients infected with organisms that are resistant to most, if not all, available options," Boucher told CIDRAP News. That includes organisms like carbapenem-resistant Enterobacteriaceae (CRE), the "nightmare" bacteria that have proven to be highly resistant to several classes of antibiotics.
Typically, the FDA requires clinical trials for new drugs to involve several hundred, perhaps thousands, of patients to determine safety and efficacy. But because the number of patients affected by multidrug-resistant organisms is small, identifying and enrolling enough participants to conduct large-scale clinical trials is difficult.
Boucher said allowing for smaller trials would make it more feasible for pharmaceutical companies to get antibiotics approved. The drugs, however, would still have to clear the normal regulatory hurdles before receiving the go-ahead from the FDA.
"There still would be comparative trials, there still would be statistics, there still would be evidence of effectiveness and safety," Boucher said. In addition, the legislation would not guarantee a shorter review time.
Boucher said there are a number of early-stage compounds that could benefit from such a pathway.
Critics warn of lower FDA standards
There is opposition to the bill. Among the critics is the watchdog group Public Citizen, which argues that the PATH Act would lower the standards for FDA approval of new antibiotics by allowing approval based on much weaker evidence than what is typically produced in large, well-controlled phase 3 trials. In particular, the group cites language in the bill that would allow the FDA to consider "alternative endpoints" and preclinical, pharmacologic, and pathophysiologic evidence in evaluating limited-population antibiotics.
"We think that if the FDA were to rely on those lower levels of evidence, that would allow potentially unsafe and ineffective drugs to come to market," Michael Carome, MD, director of Public Citizen's Health Research Group, said.
Carome also argued that the intended safeguards in the bill—such as provisions that require limited-population labeling, post-approval monitoring, and submission of all marketing materials 30 days in advance of dissemination—don't overcome their concerns.
Boucher disputes the idea that the PATH Act would lower FDA approval standards. "There would be absolutely no lowering of the standard" for FDA drug approval, Boucher said. "The standard is the standard."
