Shyam Bishen, Head, Centre for Health and Healthcare
The growing problem of antimicrobial resistance, or AMR, has been called a “silent pandemic”, a “slow-motion tsunami”, and one of the “top 10 global health threats to humanity in the 21st century”.
Antimicrobial resistance happens when bacteria, viruses, fungi and other microbes no longer respond to the medicines (antibiotics, antivirals, antifungals) used to treat them. It’s a natural process that occurs as the genetic make-up of pathogens changes over time, but it has been accelerated by the misuse and overuse of antimicrobials to treat humans, animals and plants.
More than 80% of global AMR deaths occur in developing nations and it leads to more deaths in the World Health Organization’s (WHO) Africa Region than anywhere else in the world.
By 2050, it’s thought AMR could kill as many as 10 million people, with the global costs estimated to reach $100 trillion, resulting in a 3.8% drop in global GDP, according to Investor Action on AMR (IAAMR).
AMR: The Road To UNGA 79
On 26 September, the United Nations will convene an AMR High-Level Meeting.
This is the second time such a meeting has taken place at the UN General Assembly (UNGA). The first, in 2016, resulted in the adoption of a political declaration recognizing that “prevention and control of infections in humans and animals are the key to tackling AMR”.
In the lead-up, British economist Jim O’Neill reviewed AMR’s global implications, recommending “incentives to develop new drugs, vaccines and diagnostics”. But the Wellcome Trust, which commissioned the report alongside the UK government, says little progress has been made.
This remains a key component to tackling the AMR crisis and while there has been some innovation, there are challenges to overcome. Emerging financing models are set to play an important role.
The Dry Antibiotic Pipeline
Since 2017, only 13 new antibiotics have obtained marketing authorization, but only two represent a new chemical class and can be termed “innovative”. It typically takes between 10 and 15 years for new drugs to progress from candidate stage to clinical trials, but only two to three years for antibiotic resistance to develop.
In June 2024, the WHO’s report on antibacterial agents in clinical and preclinical development found there is a “pressing need for new, innovative agents for serious infections and to replace those becoming ineffective due to widespread use”.
There are multiple reasons for the dearth in the development of new antibiotics, but market failures play a big role, with few incentives existing for the pharmaceutical industry, low sales volumes and uncertain return on investment for investors.
The net present value (NPV) – expected profitability of a drug development project – for an antibiotic development project has been estimated at −$50 million compared to $1.15 billion for a musculoskeletal drug.
The ‘discovery void’ began when big pharma companies left the antibiotic market between 2000 and 2010, as they shifted focus towards more profitable drugs for cancer and lifestyle diseases.
Today, it’s primarily just academic institutes and small- and medium-sized enterprises (SMEs) that carry out research into new antibiotics – but they lack the funds and, increasingly, the expertise to take the compounds through clinical trials to market.
Towards Innovative Antibiotic Funding Models
This year’s High-Level Meeting at UNGA is expected to conclude with the approval of an action-oriented political declaration with a shared vision to accelerate progress.
Only 11% of countries have “dedicated funding in their national budgets for implementation of multisectoral national action plans on antimicrobial resistance”, states the declaration, which includes a commitment to dedicated financing with the goal of “at least 60% of having achieved funded plans by 2030”.
The need to “explore, encourage and promote a range of innovative incentives and financing mechanisms for multisectoral health research and development to address antimicrobial resistance” is highlighted, with public-private partnerships being central to these efforts.
In the past decade, multiple initiatives have been launched to incentivize the development of antibiotics, with the EU, US and UK leading on push funding efforts.
Although they have unlocked vital funding for R&D, as research shows, many of these initiatives focus on early-stage funding for academic and research institutes, while SMEs are just as in need of financing for clinical trial phases.
At a global level, organizations including CARB-X and the Global Antibiotic Research & Development Partnership (GARDP) are working to bridge the funding gap.
Combining Pull And Push Incentives
In June 2023, the European Observatory on Health Systems and Policies published a policy brief urging for “a holistic package of incentives” to reinvigorate the antibiotic pipeline.
It recognized the success of push incentives but called for the need to align these with pull incentives, such as financial rewards linked to R&D results, reimbursement reforms and regulatory changes, to “increase revenue and create viable markets for antibiotics”.
Addressing market factors, improving return on investment and supporting SMEs would help to align push and pull incentives, the brief noted.
There are various different pull funding models being used throughout Europe, from subscription payments and market entry rewards to transferable exclusivity extensions, and milestone payments, which guarantee grants at different stages.
In the UK, the government’s five-year action plan for antimicrobial resistance included a world-first pilot, which paid companies a fixed annual fee for antimicrobials based on an assessment of their value to the NHS.
Building on its success, NHS England is looking to establish an antimicrobial products subscription model to offer a contract with a fixed annual fee; delinked from the volume of the product used.
‘Delinkage’ is emerging as a promising model, according to ReAct – the network for Action on Antibiotic Resistance, which can “pay for Research & Development costs and remove the need to charge high prices or maximize sales volumes”.
Combining push and pull incentives in mix or hybrid financing models is widely considered the most effective way to accelerate the development and deployment of new antibiotics.
The political declaration on AMR closes with the need to convene another High-Level Meeting in 2029 to review the declaration’s implementation.
In 2029, it will be a century since Fleming’s discovery of penicillin, but without coordinated global effort, innovation and financing to end the AMR crisis now, all the progress he set in train could be undone by 2030.