Applied Clinical Trials
Peter O’Donnell explores where the EU stands today in R&D pursuits for new antibacterial therapies.
The European Union has long been one of the most energetic advocates of effective research to boost research into new antibacterial therapies, but it has just received a sharp kick in the teeth from an official assessment that its delivery has been very much less remarkable than its rhetoric. The EU’s fight against superbugs, especially bacteria that have become resistant to antibiotics, “has brought little progress to date,” said a report from the European Court of Auditors.
It is embarrassing enough that the view comes from one of the EU’s own institutions-the court is the EU’s own principal spending watchdog. What makes it more intense as a rebuke is that the auditors’ harsh judgement was issued just as the EU was preparing one of its standard expressions of support for European Antibiotic Awareness Day, which was held on Nov. 18. The timing highlighted a striking contrast between words and actions-in respect of the EU’s repeated claims to be supporting the development of new medicines in this field, and in terms of promoting rational prescribing.
“Discovering and making available new antimicrobials through research and development” is one of the main challenges on which success in the fight against AMR (antimicrobial resistance) ultimately depends, it says. But “there has not yet been any breakthrough in the development of new classes of antimicrobials,” despite the fact that the EU budget is a major source of funding for investment in AMR research-with its $1.7 billion in support for research accounting for over 99% of EU total spending on AMR since 2004. Most of this money has been directed toward the search to develop new antimicrobials, alternative treatments, and vaccines, through grant payments that are intended to “push” ideas for new drugs through development phases and ultimately to their commercialization.
Noting the familiar challenge that the antimicrobials market lacks commercial incentives to develop new treatments (“there are currently no specific ‘pull’ economic incentives such as market entry rewards and long-term supply continuity models,” the report remarks), the auditors go on to rehearse the classic diagnosis: no new class of antibiotics has become available since the 1980s, and the absence of new drugs is complicated by multiple manufacturers’ decisions to cease marketing some existing antibiotics that continue to work. It cites estimates from the EU’s main medicine research program, IMI, of costs of €1 billion to bring a new drug to the market.
Structures have been created to speed up the development of new antimicrobials, the report observes, but these EU-funded public–private research initiatives have experienced delays. Meanwhile, there has been no comprehensive evaluation of the EU approach to antimicrobial research, “and its action plan does not address some of the specific challenges facing AMR research: concrete initiatives to address market failures affecting provision of new antimicrobials are largely absent,” the report states.
Existing AMR efforts
The report provides insights into the EU’s AMR-related research projects. A flagship initiative, the New Drugs for Bad Bugs Program (ND4BB), launched in 2012, has a $700 million budget to help forge a public-private partnership for the discovery, development, and market entry of new antimicrobial treatments. But, here, several component projects (notably Combacte and iABC) have run into delays in using available funds.
Another, a drug discovery platform providing technical expertise for the development of antibiotics targeting gram-negative bacteria, has had some success in supporting potential candidates, but “there is a risk that the efforts to develop the five drugs still in the pipeline will slow down if the platform ends as scheduled in 2020”-since “there was no EU mechanism to finance the infrastructure after the projects’ end.” Similarly, EU budget funding is scheduled to end in 2021 for the Combacte-NET and Magnet clinical development projects that are testing promising new products that have attracted commercial interest. And a 2018 grant toward developing a new clinical trials network for emerging infectious diseases, due to start in 2021, also risks going to waste, as “there was no agreed process to maintain the infrastructures developed.” In addition, despite the EU’s avowed objective of supporting smaller firms in their R&D efforts, only about 5% of funding from the ND4BB program has been used for small and medium-sized enterprises (SMEs), the auditors found.
The EU’s action plan fails to address all of the specific challenges for AMR research, report the auditors. In particular it ignores the long timelines and challenges involved in the discovery and development of new antibiotics, and pays inadequate attention to how activities linked to long-term research priorities can be sustained across programming periods for funding.
“There are concerns about the insufficient commercial incentives for pharmaceutical companies to invest in this field,” say the auditors. They note that a 2018 EU-funded study had recommended strengthening the investment climate and pipeline for new antimicrobials by introducing “pull” mechanisms offering approximately €1 billion to successfully bring one first-of-a-kind new antibiotic to the market. But “by the time of our audit, the EU had not decided on specific initiatives to promote pull mechanisms,” report the auditors.
The auditors’ assessment ranged widely, from the rigor of surveillance of healthcare-associated infections and the spread of AMR in the environment to the promotion of prudent use in animals, but it is their evaluation of EU support for AMR research that will strike a chord with readers of ACT. Overall, “there is little evidence that the health burden of [AMR] has been reduced,” say the auditors, pointing to the annual European death toll of 33,000 from infections caused by drug-resistant bacteria, and the associated costs.
There is some sympathy for the scale of the challenges: “The delays are not surprising in a field as volatile and complex as antibiotic drug discovery and development. It is extremely difficult to pursue this kind of activity within the constraints of a traditional project-driven and grant-funding approach,” the report concedes.
But the report’s conclusion is unambiguous: “The European Commission, together with the member states, need to further step up their efforts to tackle this growing and serious threat to public health”, said Nikolaos Milionis, the auditor in charge of this report. And, unsurprisingly, one of the auditors’ key recommendations is “strengthening strategies for boosting AMR research in the EU.” By the end of 2022, the EU should come up with a plan for how to address market failures affecting the provision of new antimicrobials, they urge.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.