A coalition of drug makers, infectious disease experts, and public health advocates yesterday called on US lawmakers to pass measures that could "jumpstart" the development of critically needed antibiotics.
In a letter sent to lawmakers in the Senate and the House of Representatives, stakeholders from large and small pharmaceutical companies and organizations including the Infectious Diseases Society of America, the Pew Charitable Trusts, and Trust for America's Health asked Congress to "swiftly enact a package of incentives that would sustainably reinvigorate the pipeline of antibiotics while ensuring patient access and appropriate stewardship."
The letter, which was addressed to the leaders of the Senate Finance Committee, the Senate Committee on Health, Education, Labor and Pensions, the House Ways and Means Committee, the House Committee on Energy and Commerce, and the House Subcommittee on Health, says some of the incentives must be passed in 2019 to meet patient needs and "help mitigate a public health crisis."
Calls for government action
The letter adds to the growing calls for government action to address antibiotic resistance, which is threatening many of the current antibiotics used to treat serious bacterial infections, and the dearth of new antibiotics. Of the 42 antibiotics currently in clinical development—a fraction of the 1,000-plus cancer drugs currently in development—only 11 target the pathogens on the World Health Organization's list of priority pathogens. And perhaps only two of those candidates will make it market.
The main issue is the lack of economic incentive for making new antibiotics. Compared with medicines for chronic conditions, which patients may have to take for many years, antibiotics are used for a short period of time. In addition, since most current antibiotics still remain effective, new antibiotics are kept in reserve to prevent development of resistance. Because the current drug reimbursement system links profits to the volume of drugs sold, this means that pharmaceutical companies don't get a significant return on their investment in new antibiotics.
As a result, many large drug makers—including AstraZeneca, Sanofi, and Novartis—have abandoned their antibiotic development programs in recent years in favor of more lucrative drugs. Only a handful of large pharmaceutical companies remain in the antibiotic development space.
And while there are many small biopharmaceutical and biotech companies working on new antibiotics, with financial support from government agencies like BARDA (the Biomedical Advanced Research and Development Authority) and public-private partnerships like CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), these companies lack the financial resources to get drug candidates through late-stage clinical development and Food and Drug Administration (FDA) approval and on to the market.
To address these challenges, many antibiotic development advocates believes new incentives are needed. These incentives, the group writes, could include a mix of tax incentives, novel "pull" incentives that increase the value of new antibiotics, and changes in how pharmaceutical companies are reimbursed for antibiotics.
"We, the undersigned, believe the solution requires a package of incentives that address both the short-term need to stabilize the market and policies to address the broken market that makes antibiotic development economically infeasible for both small and large companies," the letter states. "The ultimate goal is to create an ecosystem that supports sustainable discovery, development, and commercialization of novel, innovative antibiotics in order to preserve these vital drugs and health care advances they make possible."
New reimbursement models
One potential idea to delink profits from the volume of antibiotics sold was presented by FDA Commissioner Scott Gottlieb, MD, in September 2018, when he announced the agency's strategy for fighting antibiotic resistance. Gottlieb suggested the development of a new reimbursement model that would combine milestone payments and subscription fees for new FDA-approved antibiotics that have high clinical and social value—such as drugs that target multidrug-resistant organisms. The subscription fees for access to the new drugs would be priced to create a sufficient return on investment.
Gottlieb said this idea and other potential payment strategies, which would be linked to the promise of effective stewardship efforts by hospital and drug makers, are being discussed with the Centers for Medicare and Medicaid Services.
Other governments are considering similar ideas to spur antibiotic development. Last week, the British government announced that it will launch a pilot program in which the National Health Service will experiment with buying an antibiotic "service" from pharmaceutical companies, paying them up-front for access to effective new antibiotics.
Among the other pull incentives that have been previously suggested are market entry rewards, in which companies would receive a large up-front payment for development and approval of a critical new antibiotic. DRIVE-AB, an international consortium of public health organizations, academic institutions, and pharmaceutical companies, last year proposed a market entry reward of $1 billion for regulatory approval of a new antibiotic, with funding coming from governments and philanthropic organizations.
The letter suggests that any pull incentive package approved by Congress should require that incentives be paid after FDA approval, should aim both to stabilize the current market for new antibiotics and ensure viability of future development, should provide predictability for drug developers, and should be aligned with appropriate antibiotic stewardship and surveillance.
Feb 5 antibiotic incentives letter
Sep 14, 2018, CIDRAP News story "FDA plan focuses on antibiotic development, stewardship"