“Transferable exclusivity voucher: a flawed incentive to stimulate antibiotic innovation”, The Lancet, 9 February 2023: EFPIA-BEAM Rejoinder
17.02.23
Antimicrobial resistance (AMR) is widely acknowledged as a significant global health threat, and the inadequate global investment in developing new antimicrobials due to a lack of policies addressing market failure is a recognised issue. The resulting gradual breakdown of the antimicrobial research and development (R&D) ecosystem, propelled by the financial struggles of small and medium enterprises that are spearheading most of the new treatment R&D, presents a catastrophic threat for our societies.
The article by Årdal et al.[1] published in The Lancet on 9 February 2023 is the latest addition to the substantial scientific literature highlighting the scarcity of development programmes in the antibiotic pipeline and the underlying causes of market failure. The article sets out to critique the Transferable Exclusivity Voucher (TEV), one of the policy solutions considered to replenish the antibiotic pipeline. In their commentary, the authors first argue that the TEV concept has not been tested and should therefore be rejected. The lack of testing of the TEV is a common feature of any novel policy solution, including the multi-country revenue guarantee supported by the authors. The article presents several additional claims, a number of which require correction.
1. The authors argue, “there is little public health need for three new antibiotics every year”. The need for new antibiotics is in fact tangible and pressing. This is well illustrated by the list of priority pathogens maintained by the WHO, for which new antibiotics are urgently needed.[2] The authors further consider that attempting to address these gaps would be unrealistic, as “there are few antibiotics in clinical development that are likely to meet European public health needs.” That is exactly the problem that TEV could solve. If we are to address the challenge of AMR, we need more antibiotics in development. Rather than assuming failure, we should implement the policy solution most likely to replenish the antibiotic pipeline. We do accept however that we also need to be realistic about how quickly this can happen. Research for the pharmaceutical industry consulted a range of experts including some of the authors of the article and considered scenarios where one or two new antibiotics are developed per year.
2. The article asserts that new antibiotics will not be available, and that they “typically take years to become available in European countries after EC approval”. However, a fundamental principle of the TEV concept is that it would decouple the incentive for the antibiotic from payment. The result is that price negotiations nationally could be accelerated. In contrast, other approaches, such as the revenue guarantee model, depend on existing national price and reimbursement processes. This is a disadvantage of the revenue guarantee model.
3. It is claimed that the TEV will not promote equitable global access to new antibiotics, contrary to the aim of the 2022 EU Global Health Strategy of “enhanced equity in the access to vaccines and other [medical] countermeasures”. Again, this is an assertion we consider to be wrong. According to research we carried out, the TEV will encourage the development of antibiotics that are vital across the globe.
4. The cost of a TEV able to effectively incentivise R&D of novel antimicrobials has been much debated. Modelling predicting the cost over a ten-year period has shown that benefits exceed costs. This takes into account the actual pipeline of products that might benefit from extended exclusivity further to a TEV, the value of particular products at the point the TEV is applied, the impact of delayed genericisation on different EU member states and that this cost is paid in the future. The difference between the published report and the simple estimates referred to in the article reflects four issues: (1) the actual products that would purchase a TEV (2) the net sales taking into account commercial rebates (3) the level of biosimilar penetration observed in practice and (4) the need to account that this would happen in the future. The article incorrectly asserts that the industry number represents an under-estimate due to “averaging”. This is not the case.
5. There is a concern that the voucher is untested and complicated. However, the idea of the voucher is not new and has been considered in a series of papers[3] and multi-stakeholder forums. It has been examined over the years by academia, the industry and the European Commission. As a result, many of the concerns expressed in the article have been raised and solutions discussed.
6. It is argued that a TEV could have detrimental effects on the development of biosimilars. Given time-consuming and expensive development pathways, the industry recommends that a TEV can only be applied to a product with two years remaining of its existing protection. This should mitigate concerns regarding predictability.
Every model has its advantages and disadvantages. Introducing a scheme such as a revenue guarantee in every member state to ensure a sizeable and predictable incentive for sustainable R&D in antibiotics, as proposed by the authors, is complicated, would take many years (which we do not have) to set in motion, and is likely to be inadequate to effectively direct greater R&D efforts in antibiotics. We need action now to find solutions in the interest of global health.
[1] Transferable exclusivity voucher: a flawed incentive to stimulate antibiotic innovation. www.thelancet.com Published online February 9, 2023, https://doi.org/10.1016/S0140-6736(23)00282-9
[2] https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed
[3] A framework for assessing the potential net benefits realised through Transferable Exclusivity Extension (TEE) as an incentive for development of novel antimicrobials: FINAL REPORT; https://www.efpia.eu/media/676634/cra-efpia-a-framework-for-assessing-the-costs-and-benefits-of-tee-final-report.pdf