FDA Launches Major Push for New Antimicrobials

The critical need for new medicines to combat infectious diseases that fail to respond to current medical treatment is prompting FDA to join with other federal health agencies and the biomedical research community to advance the science, regulatory policies and reimbursement strategies to support innovation in this area. A main problem is that current payment and coverage policies for new drugs encourage widespread use of the product to generate a sufficient return on investment to companies sponsoring research on new treatments. But to remain effective against lethal  pathogens, new antimicrobials need to be used very sparingly, cutting revenues in the process.

These financial obstacles have curbed industry investment in developing new antimicrobials. The Pew Charitable Trusts reports that as of June 2018 only 42 new antibiotics were in clinical development to treat serious bacterial infections. Just one in 5, moreover, are likely to succeed, and only a handful have potential to address serious resistance problems, such as  gram-negative bacteria, which cause particularly hard-to-treat infections.

To address this crisis, FDA commissioner Scott Gottlieb recently unveiled a 2019 Strategic Approach for Combatting AMR (antimicrobial resistance) at a meeting September 14, 2018 organized by Pew. The plan includes policies and programs to encourage development of new drugs, diagnostic tests and vaccines; to promote responsible stewardship of antimicrobials in animals and humans; to improve surveillance of antimicrobial use and resistance; and to advance research for developing new tools, standards and policies in this area.

Reimbursement critical

Key to spurring innovation in this field is to devise new reimbursement strategies to support the development of products that would be prescribed and used on a highly limited basis. In a June statement, and again at the Pew conference, Gottlieb outlined proposals for devising innovative milestone payments and subscription fees for developers of products targeted at multi-drug resistant organisms. To maintain a robust pipeline for antibiotics, Gottlieb recognized the need to “change the perception that the costs and risks of antibiotic innovation are too high relative to their expected gains.” One proposal is a subscription-based model that charges hospitals a flat rate or licensing fee for access to a certain number of doses each year of a new antimicrobial. By creating a predictable revenue stream, this kind of “pull incentive,” Gottlieb explained, would “create natural markets for drugs targeted to rare but dangerous, multi-drug resistant pathogens that can threaten human health.”  

FDA is working on pilot programs or demonstrations of such reimbursement strategies with the Centers for Medicare and Medicaid Services (CMS) and other health and research agencies, such as the Gates Foundation, the Center for Medicare and Medicaid Innovation, and the Biomedical Advanced Research and Development Authority (BARDA), along with insurers and payers. These might include add-on payments for new technology, including antibacterials drugs that meet public health needs.

FDA’s initiative for combatting AMR also includes a new five-year plan to support antimicrobial stewardship in veterinary settings. A main aim is to curb the use of antibiotics to promote animal growth. Another part of FDA’s plan involves improving surveillance of antibiotic use in humans and animals to track infections more quickly and help determine when antibiotics should be used and then discontinued. This involves refining standards for transmitting data on antimicrobial sales and on-farm product use. Equally important is support for developing in vitro diagnostics able to detect disease rapidly, identify appropriate treatment, and track resistance. FDA also seeks to clarify standards for transmitting lab test results related to antimicrobial use and resistance.

To advance regulatory science in this area, the Office of Antimicrobial Products in the Center for Drug Evaluation and Research (CDER) has requested input from stakeholders on developing an annual list of science initiatives likely to spur development of new antimicrobial products. In June, FDA issued draft guidance to help manufacturers utilize the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) in developing new therapies. The program was authorized by the 21^st Century Cures Act, but has been challenging for both sponsors and FDA to implement. The guidance describes how sponsors may seek approval of qualifying treatments for small numbers of seriously ill patients based on data from smaller, shorter or fewer clinical trials.

In addition, the Center for Biologics Evaluation and Research (CBER) is promoting development of non-traditional alternatives to small molecule drugs, including bacteriophages, live biotherapeutics and fecal microbiota for transplant. CBER also is exploring vaccines to prevent infections caused by microbes resistant to current treatment, which ideally would reduce the risk of infections that require treatment with new antimicrobials.