New AMR Report Is ‘A Wake-Up Call’, Says Industry Body
Low Investment, Lack Of Incentives Seen As Key Problems
Executive Summary
Another day, another report on how to tackle the ever-present problem of antimicrobial resistance and the dearth of new treatment. In its latest assessment of the state of play, the AMR Industry Alliance has come up with some alarming facts and figures – and some ideas for the next steps.
“The battle against the growing challenge of AMR may well be won or lost in the next decade.” That is the stark warning voiced by Professor Dame Sally Davies, a former chief medical officer for England and now the UK’s Special Envoy on Antimicrobial Resistance.
Governments, industry and other stakeholders “must work together, pulling out all the stops to put in place more effective regulations, improve market mechanisms and incentive systems, leverage existing stewardship and prevention strategies, and further strengthen public-private partnerships,” Davies says in the foreword to a new report on progress made in tackling AMR over the past few years.
The report is the second to be produced by the AMR Industry Alliance, a body representing more than 100 life science companies and associations. It is based on responses to a survey from 65 of the 91 eligible members (compared with 37 of 101 members in the 2017 survey). It is also the latest in a long line of reports, reviews and recommendations to be published on the long-running battle against the recalcitrant microbes that are responsible for knocking out some of the most important pharmaceutical defences against infection.
In the past year alone, initiatives on this front have included a CDC report on the rise of projected AMR infections in the US, a report from the UN Interagency Coordination Group (IACG) on AMR on improving appropriate access to antibiotics, and the Council of the EU’s conclusions on making the EU a “best practice region” in tackling AMR.
In October 2019 a review of “Progress on Antimicrobial Resistance” by think tank Chatham House highlighted a “startling lack of progress on critical recommendations to tackle antimicrobial resistance.” Most recently, the European Commission announced it was looking into new ways of addressing the antimicrobial drug market failure. (Also see "EU Looks At New Ways To Tackle Antibiotic Market Failure" - Pink Sheet, 8 Jan, 2020.)
“There has been no progress in addressing the economic drivers of declining private investment in antibiotic R&D” – AMR Industry Alliance Report
There may be a lack of new antibiotics in the pipeline, but there is clearly no such dearth of proposals for tackling the problem. So what does the AMR Industry Alliance’s latest 112-page tome have to offer?
Well, it states bleakly that there has been no progress in addressing the economic drivers of declining private investment in antibiotic R&D, such as valuation, reimbursement, and incentivization. Since the first progress report, it notes, three large research-based pharmaceutical companies have publicly exited antibiotic R&D, the latest being Novartis in 2018.
And while there have been some positive signals – such as the UK’s 2019 plan to pilot a subscription-style payment model and the US Centers for Medicare & Medicaid Services reforms to reimbursement of novel antibiotics – it says that “no country has yet made fundamental changes to the way antibiotics are reimbursed or valued.” Not only that, “no progress has been made by any governments in the implementation of novel market-based pull incentives.”
“Worryingly,” it continues, “low levels of investment for later and more costly stages of R&D for AMR-related products may mean that many promising early-stage compounds will never reach patients unless governments put in place new mechanisms and incentives for antibiotic development.”
So far, so bad. Thomas Cueni, chair of the alliance, said the findings in the report should be “a wake-up call as the reported investment of US$1.6bn in 2018 in AMR-relevant R&D is likely insufficient to sustain a viable pipeline.” However, Cueni declared that the alliance was “making progress on its manufacturing commitments as well as in securing better access to life-saving antibiotics for patients all over the world” and that there were “good reasons to be optimistic about the Alliance’s active and growing engagement with AMR.”
Cueni told the Pink Sheet that companies reported taking "a wide range of measures to promote appropriate use of antibiotics in order to slow the emergence of resistance, prolong the effectiveness of antimicrobials and improve patient outcomes." He added that the alliance was "leading on the issue of responsible manufacturing of antibiotics, establishing an industry standard for reducing potential environmental risks from antibiotics production two years ahead of schedule."
Collaboration and the formation of a "coalition of the willing," taking on the task of stopping AMR from becoming one of the worst public health emergencies to date, will be key in the years to come, Cueni said.
Recommendations
The report makes a number of recommendations as to how alliance members and the broader life sciences industry can contribute further to the global response to AMR. This includes “accelerating the sharing of data to promote innovation and making surveillance data publicly available, including data on infection rates, AMR patterns, and antibiotic use.”
It also “proposes areas where new or deeper partnerships with governments, patients, and providers are required, such as improving market conditions necessary for sustainable development and commercialization of novel solutions to AMR, and strengthening local healthcare and laboratory capabilities to support effective diagnosis and treatment of drug-resistant infections.”
On the regulatory front, the report says the alliance will continue to press governments to implement policy reforms that would “create market conditions that support sustainable investment into and commercialization of AMR-relevant R&D as well as diagnostics, vaccines, improvements to existing therapies, complementary technologies, and novel solutions.” This could include piloting new payment mechanisms and pull incentives.
It also promises that companies will work with health systems “and the broader pharmaceutical industry to ensure that vaccines, diagnostics, novel antibiotics, and other AMR-relevant products are appropriately valued.”
Access
A key piece of advice is that companies should partner with governments and NGOs to remove “regulatory burdens that may otherwise reduce broad global registrations of critical antimicrobials,” and to pilot new payment and reimbursement mechanisms that allow appropriate patient access to antimicrobials.
“Investment levels may further decrease in the coming years if governments do not take urgent action to improve antibiotic reimbursement systems and implement new incentives for development,” it declares.
“Until a package of incentives [is] introduced, private investment into antibiotic development is likely to continue to decline” – AMR Industry Alliance Report
While some novel reimbursement approaches have been proposed, notably in Sweden, the UK and the US, they have not yet been implemented, the report notes. “Until a package of incentives, including reimbursement reform and novel pull incentives to address the well-documented economic challenges in the antibiotic market, are introduced, private investment into antibiotic development is likely to continue to decline,” it says.
Nonetheless, it said that 81% of respondents said they had developed comprehensive strategies to improve access, and 63% had partnerships with governments, NGOs, industry trade groups and local healthcare bodies to expand access to AMR-relevant drugs.
Appropriate Use
AMR is of course abetted by poor prescribing and consumption practices.
Cecilia Ferreyra, AMR medical officer at the Foundation for Innovative New Diagnostics (FIND) in Geneva, Switzerland, said there was “an urgent need to preserve existing (and new) antibiotics by developing and implementing more robust user guidelines.” Ferreyra said donors and governments would need to “provide greater support in appropriate prescribing practices in countries, communities, and hospitals, with particular emphasis on making the right tools available and accessible in low-resource settings.”
The life sciences industry, including many AMR Alliance members, collects and uses surveillance data to identify and better understand resistance patterns for a number of pathogens,” according to Ferreyra. “The private sector should expand these efforts and explore potential partnerships, including with governments, to improve data transparency.”
The next steps in this area, says the report, are to scale up educational activities and promote the use of smarter prescription tools that are adapted to local contexts, increase sharing of AMR surveillance data by alliance members, and support initiatives to increase public reporting of infection rates, antimicrobial resistance patterns, and antibiotic use.
Manufacturing And Pollution
Another contributor to growing AMR rates is antibiotic pollution of the environment, particularly drinking water, as a result of human and animal excretion and discharges from pharmaceutical plants and hospitals.
In 2018, manufacturing members of the alliance developed the Common Antibiotic Manufacturing Framework for environmental management of antibiotic manufacturing. This offers companies a methodology for conducting risk assessments, and sets out the minimum site requirements to meet environmental standards.
By June 2019, 83% of the alliance’s manufacturing members had assessed all of their owned sites against the framework, the report says, and other organizations have begun adopting the same standards. For example, Medicines for Europe, the trade association for European generic and biosimilar companies, has made membership conditional on a company’s commitment to the framework and predicted no-effect concentration targets.
Cueni said: "As next steps, the Alliance has set out to accelerate the implementation of the framework across all its members’ supply chains. Across sectors, companies predict that they will meet the framework’s requirements within the next three years, while another 35% of companies would meet it within four to seven years."
Alistair Boxall, Professor of Environmental Science at the University of York, UK, said the manufacturing framework and discharge targets marked “a significant step forward in reducing antibiotic impacts in the environment.”
These initiatives, he said, were already having an impact: 34% of owned and supplier sites now meet or partially meet framework requirements, and production processes for 92% of products across all sites are expected to meet the discharge targets within the next seven years.
However, Boxall said there was “still work to do to ensure full adherence to the framework within this timeframe.
“Alliance members must continue to refine and update the framework and targets as new scientific knowledge becomes available; and should work to encourage non-member manufacturers to adopt the new standards.”
“All stakeholders… must make combating this complex public health challenge one of their highest priorities” – Professor Dame Sally Davies, UK Special Envoy on Antimicrobial Resistance
The report also looks new products that are in the pipelines of alliance member companies. It includes a number of case studies such as Scynexis’s development of ibrexafungerp for Candida auris, a new multidrug-resistant fungal species, and Summit Therapeutics’ ridinilazole for Clostridioides difficile infections of the bowel, as well as a Janssen vaccine in development for infections cause by extra-intestinal pathogenic Escherichia coli.
The last word goes to Davies, who is also co-convener of the UN Interagency Coordination Group on AMR (IACG): “As we enter a new decade, AMR is spreading faster than ever, and all stakeholders – including governments, the life sciences industry, academics, healthcare providers, philanthropic donors, and the public health community – must make combating this complex public health challenge one of their highest priorities. Business as usual is simply not an option.”
Davies said it was important to look for novel multisectoral, public-private partnerships and stronger engagement between organizations and different sectors of the life sciences industry.
“Finding ways to accelerate R&D investment, expand access to quality-assured antimicrobials and vaccines, and promote novel diagnostic tools and technologies as a means of cutting unnecessary use is of utmost importance… I look to the AMR Industry Alliance to play its part at the forefront of these efforts.”