National Academies Report: New Antimicrobials Must Overcome Market Barriers Before Combating Resistant Strains

The report, prepared by the Committee on Examining the Long-Term Health and Economic Effects of Antimicrobial Resistance in the United States, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), calls for special programs to facilitate new antimicrobials entering the market, and others to target the seemingly disparate goal of decreasing their use, but thereby preserving their value.

The Committee notes that while it can take more than 10 years of on-patent sales for a new antimicrobial to achieve profitability for the manufacturer, the agent may lose effectiveness against a target pathogen, and therefore market viability in a shorter time period as resistance emerges.

"One of the key challenges in this situation is the price tag of a market entry reward program to the taxpayer, which, according to some of the recent estimates, ranges from $2 to over $ 4 billion per drug." Committee member Aylin Sertkaya, PhD, vice president and senior economist, Eastern Research Group (ERG), Lexington, MA, explained to Contagion.

"When you couple this price tag with the difficulty of assessing a new antibiotic's added clinical benefit over existing therapies and/or its ability to address a truly unmet medical need at the time of regulatory approval with an acceptable degree of certainty, a deliberative approach to formulating an optimal pull incentive is prudent," Sertkaya added.

There is, therefore, a need for both "push" incentives to assist with, and reduce cost of research and development, and "pull" incentives that help transition the product from investigational to marketed therapeutic and to sustain that utility.

The committee points out that push incentives are more than direct research funding, and also include tools and information in the public domain and investments in scientific training.An example of the former is the Community for Open Antimicrobial Discovery (CO-ADD), launched in 2015 as a free service for researchers to use high-through-put screening for compounds with antimicrobial activity.The latter is exemplified by basic research grants from the NIAID, the sponsor of this report committee.

Examples of pull incentives specifically targeted to enhance antimicrobial development and marketing include the Generation Antibiotic Incentives Now (GAIN) Act, enacted in 2012; the Limited Population Pathway for Antibacterial and Antifungal Drugs, enacted in 2016 as part of the 21st Century Cures Act. In addition, revisions in 2019 to the Centers for Medicare & Medicaid Services' (CMS's) New Technology Add-On payments which, as of 2019, provide for an increased reimbursement through the Inpatient Prospective Payment System (IPPS) from 50 to 75% for all antimicrobials qualified as infectious disease products.

The 2018 Re-Valuing Anti-Microbial Products Act (REVAMP) is one of 2 bills currently pending in Congress that would provide legal and regulatory incentives for antimicrobial manufacturers. The committee speculates, however, that the failure of Congress to take action since its 2018 introduction may indicate that it is not a priority and that it may not be revisited.

A second bill, introduced in 2019, the Revisions to the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms (DISARM) Act, would allow CMS to reimburse antimicrobials qualified by the FDA separately, in addition to the bundled payments determined by diagnosis. The committee notes the intent to increase reimbursement for those antimicrobial products expected to have limited patient markets and short treatment durations.

The committee cautions, however, that "well-intentioned, recent pull incentives have not brought about the changes intended." One reason for this, according to the committee, is that the eligibility for qualified antimicrobial can be defined too broadly.

"New antimicrobials that do not necessarily satisfy an unmet need can qualify for fast track approval and extended exclusivity protections afforded as a qualified infectious disease product," the committee points out.

Sertkaya emphasized the importance of research and resources being directed toward unmet needs, rather than production and marketing of new products with little advantage.

"Developing target product profiles (TPPs) that lay out the desired characteristics for a new antibiotic and better aligning incentives, especially pull incentives, with these TPPs has the potential to address the mismatch between the existing antibiotic pipeline and the antibiotics needed to address urgent critical needs moving forward," Sertkaya said.

To read the previous story in our series on the National Academies report, click here.