What is one of the greatest challenges in infectious diseases today? If you stop someone in the street and ask them this question, they might say “COVID-19”. Or perhaps, depending on where you are, they would argue for malaria, Tuberculosis or Ebola.

All the above have a strong case, but to me, the answer that is too often missing from the conversation is antimicrobial resistance (AMR). According to the ECDC, resistant bacteria cause 33000 deaths in the EU every year and AMR is forecast to kill 10 million people by 2050. A recent study found that there were an estimated 4,95 million deaths associated with bacterial AMR in 2019. AMR threatens to undermine decades of medical progress that provides a foundation for applying medical science to improving people’s lives in a wide range of disease areas.

This hit home when I attended the 6^th AMR Conference (6 & 7 April) in Basel, Switzerland. On this occasion, I took the opportunity to advocate for policies that will ensure we meet the needs of the patient and provider community, and in particular a much-needed package of incentives that could unblock the R&D pipeline.

Reinventing antibiotic development models

The scale of the challenge is worth recalling in brief. There are simply too few antibiotics in the pipeline. According to the World Health Organization, there are 43 antibiotics targeting priority pathogens in development[1]. This is on top of a pipeline that has underperformed over the past several decades, with the last new class of gram-negative antibiotics being brought to patients in the 1980s. This is plainly insufficient to solve the problem patients, providers, and the public health community face. Compare that with neurology, for example, where there are 1320 compounds in the pipeline. Something is not working.

The obstacles to dramatically boosting progress in this field are, in part, scientific. Developing an antibiotic is hard: bacteria evolve constantly; resistance is unpredictable; trials are complex.

However, the bigger issue is that the traditional economic model for drug development is ill-suited to antibiotics. Any new antibiotic should be used appropriately and ideally left on the shelf as a last-resort option, to slow down the development of resistance. While this should not change, and stewardship should be fostered, this also requires the specificities of the antimicrobials market be considered when designing incentives to foster innovation.

Indeed, what must change is the way we value and reward breakthroughs that deliver new tools to fight AMR. 

Funding research and rethinking incentives

In a sign of its commitment to solving the problem, the global innovative biopharmaceutical industry has created the AMR Action Fund, that will invest more than USD1 billion to support the clinical development of novel antibiotics, with the goal of bringing two to four new antibiotics to patients by 2030. The AMR Action Fund has focused on identifying investments that will yield urgently needed treatments and catalyse long-term innovation to tackle AMR and on 4 April 2022, the Fund announced its first investments.

While these efforts are necessary and welcome, they are not a sustainable solution. Further action needs to be taken by governments by introducing effective pull incentives. The Fund supports early-stage research and provides a bridge for small biotech companies, but does not support late-stage trials. More profound policy shifts are still needed.

This is where the EU should take the lead. Our industry’s proposal for an effective pull incentive at EU level is transferable exclusivity extensions (TEE). It works like this: instead of extending the market exclusivity of the eligible antimicrobial, a TEE would be applied to another product – or it could be traded to another company. Rewards generated from TEE are not driving profits on other medicines, rather they are being leveraged to ensure companies can continue to invest in antibiotic research and development. Further, vouchers are only awarded after a new antimicrobial is approved, so TEE does not require an upfront government funding, and is a de-risked investment for governments and then entire health system that rely on access to effective antimicrobials. 

TEE promotes good antimicrobial stewardship by delinking financial reward from the volume of prescriptions. It reflects the societal value of delivering solutions to one of the global health challenges of our time.

The global scale of the incentive needed has been estimated at €1.8-€4.1 billion[2]. The cost of inaction on AMR is significantly higher. The OECD estimates that without significant policy interventions, AMR will lead to losses of about €2,6 trillion by 2050[3] and will result in over 569 million extra hospital days annually[4].

The idea of a TEE has been around for a while in academic circles but has only recently begun to gather momentum in the wider health policy world. Now, as we face the grave threat posed by AMR, I believe the time has come to put theory into practice. Our response must be proportional to the scale of the challenge.

As we move forward, we must work with stakeholders and focus on areas of common ground, and in this case, it is about addressing the unmet patient need. We must be bold in our actions or else we will continue to put patients at undue risk. If we all focus on the desired patient outcome, we can have the appropriate debates to advance TEE and like ideas. What we can’t do is not take any action.

[1] https://www.who.int/observatories/global-observatory-on-health-research-and-development/monitoring/antibacterial-products-in-clinical-development-for-priority-pathogens

[2] Outterson, K. (2021) ”Antibacterial R&D: Past, Present, & Future”, Available at: https://www.hhs.gov/sites/default/files/day1-03-outterson.pdf. This range will be updated in further work completed by Outterson, which will be published in November 2021

[3] https://www.oecd.org/health/health-systems/AMR-Policy-Insights-November2016.pdf

[4] https://www.oecd.org/health/health-systems/AMR-Tackling-the-Burden-in-the-EU-OECD-ECDC-Briefing-Note-2019.pdf