Congressional watchdog advises HHS to implement 'post-marketing' incentives to address dwindling antibiotic development efforts
With the Covid-19 crisis expected to shore up antibiotic use with opportunistic secondary bacterial infections — and potentially exacerbate the rate antibiotic resistance — a congressional watchdog has put together a list of recommendations to sort out the challenges affecting antibiotic stewardship, track rates of drug resistance, and fix the ‘broken’ market for antibiotics.
While bacterial pathogens mutate and grow resistant to the existing crop of antibiotics, driven by unbridled use in humans and livestock — the industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned.
The US Government Accountability Office, on Wednesday, issued a report encompassing data from documents and interviews with agency officials and experts, finding that there are various challenges in implementing appropriate antibiotic use in the United States, for instance, federal requirements for antibiotic stewardship programs apply to only certain health care facilities, and incentives for doctors to adopt antibiotic stewardship activities are optional.
The report recognized that although there is a raft of incentives in place to push drugmakers to develop antibiotics, such as funding support through the Biomedical Advanced Research and Development Authority (BARDA) and regulatory reforms such as the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) — there is a desperate need for the passage of “pull incentives,” or policy measures to increase the value of a marketed antibiotic by rewarding drugmakers only after their antibiotic is approved.
Existing incentives, “while well-intentioned…appear to have been insufficient, as they focused exclusively on bolstering the development pipeline without removing the blockage created by issues with payment,” CMS administrator Seema Verma conceded last August.
There has been a slew of bankruptcies in the antibiotic sector, as companies see their value go up in smoke as feeble sales frustrated growth. The long, arduous and expensive path to antibiotic approval — complicated by issues of clinical trial enrollment (there are no rapid diagnostic tests to identify infections, and it is hard to recruit patients in clinical trials to test antibiotics that target resistant bacteria) offers little financial gain as treatments are typically priced cheaply. The median annual sales for brand name antibiotics between 2011 and 2015 ranged from $24 million to $75 million, whereas annual sales for most new, brand-name oncology drugs were more than $500 million during the same period, the GAO report said.
For one of the biggest threats to global health, the lion’s share of antibiotic development is now taking place in a handful of labs of small biopharma companies as a majority of their larger counterparts focus on more lucrative endeavors such as oncology. Big Pharma has largely retreated from antibiotics, and only a handful remain in the space — including Merck, Roche and GSK — down from more than 20 in the 1980s.
Former FDA commissioner Scott Gottlieb, in 2018, suggested a “licensing model” in which acute care institutions that prescribe antimicrobial medicines pay a fixed licensing fee for access to these drugs, granting them the right to use a certain number of annual doses. Last year, the CMS unveiled a proposal to restructure the payment apparatus to rescue existing antibiotic manufacturers, by classifying drug resistance in a way that would compel higher payments to hospitals treating patients with antimicrobial resistance, and crafting a pathway for doctors to prescribe appropriate new antibiotics without disrupting hospital budgets. Under the current system, hospitals bundle together the costs of all the services for a given diagnosis, which tends to incentivize hospitals to prescribe cheaper, generic antibiotics that are not engineered to tackle drug-resistant infections.
The GAO made 8 recommendations fix the myriad of problems, including that the CDC should develop a plan for consolidated reports of antibiotic resistance in priority pathogens at regular intervals; the HHS should identify leadership and clarify roles and responsibilities among HHS agencies to assess the clinical outcomes of diagnostic testing for identifying antibiotic-resistant bacteria; and importantly that the HHS should come up with a strategic framework to further incentivize antibiotics for drug-resistant infections, including through the use of postmarket financial incentives.
Each recommendation apart from the postmarket financial incentives was accepted by the various agencies. “HHS noted that, while it agrees that additional incentives are needed to address the limited pipeline for novel and innovative treatments to combat antibiotic resistance, it is still conducting analyses to understand whether postmarket incentives should be included as a component of its forthcoming strategic framework to further incentivize the development of new treatments. However, HHS did not specify when its framework would be released,” the GAO report said.
The authors, however, stood by their call: “We believe our recommendation is still warranted.”