- Food and Drug Administration Commissioner Scott Gottlieb this week laid out several goals and ideas to combat the threat of antimicrobial resistance and the challenge caused by a decline in research into new antimicrobial agents.
- One major hurdle is reimbursement for new antibiotics, particularly those kept reserved for limited use against resistant bacteria. The FDA and other federal agencies are working to address the need for better economic incentives, including changing the reimbursement model for therapeutics that target dangerous multi-drug resistant infections.
- The FDA is also working to advance development of improved antimicrobial drugs by making the development process more predictable and has issued guidance to support companies using the Limited Population Pathway for Antibacterial and Antifungal Drugs.
The discovery of the first antibiotic in 1928 marked a new era in public health, with millions of lives saved.
However, discoverer Alexander Fleming predicted the development of antibiotic resistance due to misuse in his Nobel lecture in 1945. Antimicrobial resistance is today one of the biggest public health challenges globally.
In the U.S., at least two million people are infected with antibiotic-resistant bacteria and at least 23,000 people die each year, according to the Centers for Disease Control and Prevention.
Trial design and economics are just two of the challenges pharmas face. Designing clinical trials for the seriously ill, or who have been treated with a number of different antibiotics, can be difficult.
And given that any new drug for serious and resistant infections will have a limited market, or may indeed be kept as an antibiotic of last resort, the market incentives are not traditional.
To promote appropriate use of the drugs while supporting development of new agents, FDA suggested several approaches. As a first step, developers can use the qualified infectious disease product (QIDP) designation program, which provides access to fast track designation, priority review designation and potential five-year extension of exclusivity.
The FDA is in discussion with the Centers for Medicare and Medicaid Services (CMS) with a view to create a license fee-based reimbursement model for specific new antimicrobial drugs that meet a critical public health need. Rather than per prescription, reimbursement would be a fixed fee per institution for access to a certain number of doses of the drug per year.
"Adapting this licensing payment model to drugs that target dangerous, antimicrobial resistant organisms can help achieve two important public heath goals. First, such a model would create a natural market for drugs that meet certain public health criteria, by providing a predictable return on investment and revenue stream through more foreseeable licensing fees. Second, it would put the institutions fully in charge of stewardship of these important medicines," the commissioner said in a statement.
"Once they purchase the ability to access a drug, they would be stewards of its use up to a certain number of annual doses, which could be tied to the number of beds an institution has or its likelihood of encountering certain organisms."
Gottlieb sees the licensing approach as potentially offering a "pull incentive" that could create a predictable market for antimicrobial drugs meeting a narrow set of critical, public health criteria.
Antimicrobial drug development also needs smoother drug development pathways. The Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD pathway), part of the 21st Century Cures Act, could help to advance development and approval of antibacterial drugs to treat serious or life threatening infections in limited populations of patients with unmet needs.
"In reviewing an application submitted under the LPAD pathway, the FDA will consider the severity, rarity or prevalence of the infection that the drug is intended to treat. The agency will also consider the availability or lack of alternative treatment in the limited population," Gottlieb said.
The FDA has issued a draft guidance to support companies looking to use this pathway, hoping that it will lead to a more streamlined approach to clinical development, for example smaller, shorter or fewer clinical trials.