Regulatory incentives are powerful tools in the development of alternatives to antimicrobials
The European Medicines Agency's (EMA) Committee of Veterinary Medicinal Products (CVMP) recently published a reflection paper and launched a consultation on "promoting the authorization of alternatives to antimicrobials in the EU". Marie Manley (partner) and Dr Chris Boyle (associate) of UK law firm at Sidley Austin provide insight into these latest moves from authorities.
The CVMP reflection paper considers the existing measures available to support the development of alternatives to antimicrobials in the field of veterinary medicine and seeks to identify where and how these measures may be improved.
The consultation comes at a critical time when the new veterinary medicines regulations (Regulation (EU) 2019/6) are being implemented and the EMA is consulting on and refining its Regulatory Science Strategy to 2025. It is crucial for the industry to engage with this consultation and to contribute to the ongoing debate, as regulatory incentives are essential tools to stimulate the research and development of medicines particularly in areas of unmet need.
Antimicrobial resistance (AMR) is a complex global health threat affecting humans, animals and the environment. A global One Health approach to simultaneously tackle AMR across these sectors has therefore been widely endorsed. The CVMP's paper considers one important aspect of this campaign – the development of alternatives to veterinary antimicrobials – as part of the drive to reduce the global use of antibiotics.
Importantly for the animal health industry, the CVMP's paper seeks additional proposals from stakeholders on how they believe the development of alternatives to antimicrobials should be facilitated and incentivized. While the paper makes many different proposals, one surprising finding is the CVMP did not find financial or other procedural regulatory incentives, over and above those already in place, to be the most significant factor reducing industry's interest in developing alternatives to antimicrobials.
This is surprising as experience has shown in both the veterinary and human sectors, such incentives are essential to stimulate the research and development of new medicines, particularly in circumstances where the financial risks of investment are outweighed by the potential benefits.
For example, in the veterinary sector there has historically been a lack of investment and lack of availability of certain veterinary medicines particularly for minor use minor species (MUMS)/limited markets. Therefore, incentives were introduced to make the research, development and commercialization of new veterinary medicines for these markets financially viable.
Likewise, in the human medicines sector, incentives have been introduced to encourage the development of treatments for rare diseases (orphan medicinal products) and medicines for children – areas that have traditionally lacked investment because of their small market sizes. In particular, market exclusivity has been found to be the strongest incentive for industry for stimulating development of medicines for rare diseases, and introduction of this incentive in the veterinary sector could be explored, for example, for new antibiotics.
Indeed, a potential approach to reduce the use of conventional antimicrobials that is recognized in the CVMP’s paper is the development of new antibiotics as alternatives.
However, the commercial risk of developing new antibiotics is particularly high for animal health companies, and without sufficient support and incentives such development may not be possible.
This is because, in addition to the enormous scientific challenge and costs of discovering and developing a new safe and efficacious antibiotic (including additional environmental tests and residue tests for food-producing species that are not required in humans), there is a risk that the commercialization of the new veterinary antibiotic may be limited or even completely prohibited. The use of a new veterinary antibiotic would likely be restricted to minimize the development of resistance to the new product. More dramatically, the use of the new antibiotic in animals could be completely prohibited if it becomes reserved for use in humans under the new veterinary medicine regulations.
"While there are challenges ahead, there are also potentially significant opportunities. If an alternative antibiotic could be developed that is effective in animals but is not suitable for use in humans, it would have the potential to be very successful commercially."
The uncertainty created by the pending list of antibiotics to be reserved for use in humans is therefore creating a further major challenge for industry (although guidance has been issued on the selection criteria and there is an open call for data on the use of antimicrobials in connection with the determination of the reserved list).
With such high commercial risks, it could well be that the available incentives will be insufficient to drive the development of new antibiotics in the animal health sector. Indeed, even in the human field, fewer companies are prepared to take on the risk of developing new antibiotics, and there have been cases where promising companies that have tried have become bankrupt.
While there are challenges ahead, there are also potentially significant opportunities. For example, if an alternative antibiotic could be developed that is effective in animals but is not suitable for use in humans, it would have the potential to be very successful commercially. While some may argue that such a product should be used as a last resort, it has also been suggested that such a product could be used as a first line of treatment in animals to decrease the pressure placed on conventional antibiotics being used in humans.
Further opportunities could also be found in developing alternative commercial models for existing and new antimicrobials that would reward industry for the societal value of their products without relying on volume of sales to drive revenue. Another proposal that has been raised is to adapt the benefit/risk evaluation of new medicines as part of the marketing authorization procedure to take into consideration the benefits that the new medicine could bring to reduce AMR.
It is important for industry to continue to engage in the ongoing consultation processes in relation to the new veterinary regulations and the efforts to tackle AMR – including in response to the CVMP paper.
Regulatory incentives are powerful tools that can stimulate R&D and are therefore critical when animal health companies weigh the risks of making substantial financial and resource commitments to develop new alternatives to antimicrobials.
The industry and regulators should carefully consider whether available incentives are sufficient to make the development of alternatives to antimicrobials viable, and as suggested by the CVMP, there should be a call for wider engagement with the EU Medicines Regulatory Network to enable such incentives to be developed and implemented.