A review of antimicrobial resistance (AMR), commissioned by the UK and led by internationally renowned economist Jim O'Neill, is calling for billions of dollars in new funding intended to incentivize drug development and head off the threat of drug-resistant disease.
Health authorities are increasingly citing AMR as one of the most pressing threats to global public health. In its 2014 Antimicrobial Resistance: global report on surveillance, the World Health Organization called AMR "so serious that it threatens the achievements of modern medicine."
The rise of AMR is associated with the overuse and misuse of antimicrobial medicines such as antibiotics. When microbes targeted by a drug are not eliminated, treatment-resistant strains can be spread, which can have deadly consequences.
The problem is compounded by a significant decline in the development of new antimicrobial drugs in recent decades. The danger this can pose can be seen in the case of drug-resistant gonorrhea, where over time strains of the bacteria have developed resistance to many previously effective treatments, leaving health authorities to resort to last-line treatments against resistant strains. Now, strains are emerging that are resistant even to last-line treatment options.
Drug-resistant strains of other disease, such as tuberculosis, malaria, HIV and E. coli are also on the rise, posing an ever-increasing threat in developed and developing countries alike.
In July 2014, UK Prime Minister David Cameron announced a review on AMR, funded jointly by the government and The Wellcome Trust, a private international aid organization, headed by economist and former Goldman Sachs Asset Management CEO Jim O'Neill.
The aim of the review was to analyze how antimicrobials are developed, used and regulated, and to propose new and innovative mechanisms to stimulate the development of new products to target drug-resistant diseases.
Now the review has released its first proposal to address the threat of antimicrobial resistance in a policy paper published this week, Securing New Drugs for Future Generations: The Pipeline of Antibiotics.
The reviewers chose to focus their efforts on drug-resistant bacteria first, citing WHO's claim that antibiotic resistance is the "single greatest challenge in infectious diseases."
The reviewers also point to differences in the market for antibiotics that disincentivize research and development, which has led to a freeze in the pipeline for new antibiotics. According to a study by the Pew Charitable Trusts in December 2014, there are only a few dozen antibiotics in development for the US market. Anyone familiar with drug development will know that most of these products will never make it to market, and ones that do "may not prove successful in clinical practice."
Proposed Payment Models
To promote the development of new antibiotics, the review calls for a new approach to incentivize research and development that would "de-link" profitability from sales. This would be done by establishing a fund to give lump-sum payments to companies that develop high-priority antibiotics. Under this single global buyer model, companies would give up the rights to market their product in exchange for a lump-sum payment when the product is licensed.
The reviewers also discuss an alternative model, combining a free-market approach with payment-incentivized development. In this model, companies would retain their rights to market their products, but would receive payment from the global fund "according to their value to society."
To actually head off the threat of AMR, the reviewers say there should be about 15 new antibiotics reaching the market each decade. Within this model, at least two new broad-spectrum and two new targeted therapeutic classes should be developed, with the rest being follow-on products in various classes. Achieving a pipeline of this magnitude will cost anywhere between $16 and $37 billion (USD) over 10 years, the reviews say, which is far less than what it costs to treat drug-resistant infections each year in the US alone.
Funding Early-Stage R&D
The reviewers also emphasize the need for funding early-stage, innovative, research and development through the creation of a "Global Innovation Fund for AMR." The reviewers look to the global pharmaceutical industry to contribute to the fund, which they say will need $2 billion (USD) over the next five years.
The fund, the reviewers say, would provide a much-needed influx of funding for high-risk projects that may deter commercial investors despite their potential to address serious gaps in the fight against AMR. Funding in this manner could help high-value projects, such as reviews of existing antibiotics and other drugs, so-called "resistance breakers," which can extend the usefulness of existing antibiotics.
The reviewers also call for increasing research into "the mechanisms by which drug resistance develops," and promoting the development of diagnostics that would allow prescribers to more closely target infections and lessen the effect of misusing antibiotics.
The reviewers are clear that their proposal is only the beginning of what is sure to be a long battle against AMR.
For their proposals to be successful, the reviewers say there must be buy-in from the both the global community and the pharmaceutical industry, as well as significant funding from governments and industry. Over the next year, the reviewers say they will be meeting with government officials and members of industry to continue to develop their proposal into a "detailed plan of action."
The proposal comes only days after advocacy groups Médecins Sans Frontières (MSF) and the Drugs for Neglected Diseases initiative (DNDi) issued a similar call for a globally funded research and development framework to address AMR and emerging infectious diseases such as Ebola.
Securing New Drugs for Future Generations: The Pipeline of Antibiotics