The Wrong Remedy: What Proposed Pull Incentives for Antimicrobial R&D Ignore About Antimicrobial Resistance (AMR)

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Ava Alkon, Global Health Advocacy and Policy Advisor, MSF USA
Dušan Jasovský, Antimicrobial Resistance Pharmacist, MSF Access Campaign
Shailly Gupta, Senior Communications Advisor, MSF Access Campaign

Ahead of the second UN High-Level Meeting on antimicrobial resistance (AMR) scheduled for September 2024, member states are negotiating a political declaration meant to strengthen and accelerate the world’s response to address drug-resistant infections — a global health crisis that is taking millions of lives and threatening decades of medical progress.

As a medical humanitarian organization that has treated thousands of people with drug-resistant infections, and one that actively addresses AMR in our projects around the world, Médecins Sans Frontières/Doctors Without Borders (MSF) sees an urgent need to strengthen the ability of health systems worldwide to prevent, detect, and respond to drug resistance. Among other measures, this requires more international support to improve infection prevention and control and antimicrobial stewardship, expand microbiological laboratory capacity, and ensure patients have access to the diagnostic tests and antimicrobials they need — both older and new ones.

Alarmed by a dearth of promising novel antimicrobials in the development pipeline, high-income country governments are now considering making major new financial commitments to stimulate research and development (R&D) for treatments to fight drug-resistant infections. While novel treatments are just one piece of the picture of what is needed for the world to get ahead of AMR, we agree that the fact that so few are forthcoming is of great concern.

A report released by the World Health Organization (WHO) in June 2024 indicated that recently approved antibacterial agents and those in the clinical R&D pipeline continue to fall far short of what is needed to counter the escalating threat of AMR.

And indeed, existing treatments are failing fastest in contexts like those where MSF provides care because low- and middle-income countries (LMICs) bear the highest burden of AMR, and humanitarian settings are at especially high risk.

We are gravely concerned, however, that some methods currently proposed for incentivizing R&D will actually prevent timely and equitable access to new treatments for people who need them the most and divert resources away from other necessary measures.

Pulling pharma back into antimicrobial R&D

The sparsity of new antimicrobials reflects, in part, the fact that multinational pharmaceutical corporations have mostly withdrawn from developing such drugs in recent decades. They do not see antimicrobials as lucrative enough to bother with due to a combination of factors.

First, antimicrobials need to be carefully stewarded in order to preserve their efficacy. Second, unlike blockbuster drugs for chronic conditions, they are often used over relatively short periods of time. Finally, they are currently needed in the largest volumes in relatively low-resource communities, which offer a limited potential for maximizing profits.

The drugs also present thorny challenges for moving from preclinical into clinical research, including finding sufficient numbers of patients with specific drug-resistant infections to enroll in trials. Boosted by public and philanthropic grants (known as “push” funding), small and medium-sized corporations have stepped into the vacuum of early clinical development of antimicrobials but frequently struggle to move past this stage due to the commercial and scientific barriers.

As a result, governments are now trying to lure major companies back into antimicrobial R&D with what are known as “pull incentives” — rewards that drug developers earn by bringing new drugs to market. What concerns us is that the pull incentives that are being launched or considered tend to preserve and/or bolster the standard model for incentivizing R&D, in which the private sector’s pursuit of profit — secured through patent monopolies, high-volume sales, and/or high prices — is the primary driver of innovation. This model is especially ill-suited to antimicrobials because these drugs must be introduced in a responsible way and used judiciously to preserve their efficacy and at the same time are needed right away in low-resource contexts that struggle to access costly new tools.

We are concerned that government incentives that further extend monopolies, boost drug prices, or provide certain other kinds of unconditioned market-entry rewards and guarantees will make lifesaving new antimicrobials less affordable and restrict access. High prices that constrain access for communities that need these drugs cannot be justified as a tool for antimicrobial stewardship.

MSF supported the Ministry of Health in Nigeria by supplying antibiotics for patients during a diphtheria outbreak in Kano, Nigeria, 2023. Photo credit: Georg Gassauer/MSF

Affordability and access concerns

Our concern is rooted in the affordability and access challenges for new drugs we have witnessed for decades in LMICs. For instance, bedaquiline, a breakthrough medicine for drug-resistant tuberculosis (DR-TB), remained largely inaccessible in most countries with a high TB burden for up to a decade following its introduction by the US corporation Johnson and Johnson (J&J) in 2012. Despite the medicine having been developed predominantly through public money (the US government’s investments exceeded J&J’s by up to five times), the vast majority of people who needed it could not afford it. The sobering story of bedaquiline in turn closely resembles previous experiences with new drugs for HIV and hepatitis C, where patents and high prices kept lifesaving treatments out of reach for years.

The limited number of new antimicrobials that have reached the market in recent years have likewise followed the same pattern. Cefiderocol, for example, an antibiotic introduced in 2019, costs $1,434 per one day of therapy in the US. While concerns about constrained and delayed access for LMICs led the non-profit Global Antibiotic Research and Development Partnership (GARDP) to broker an arrangement that will make it more affordable, civil society and patient activists battling for access for every new medicine, one by one, is not a tenable way to achieve timely or comprehensive access for people who have an immediate need for such drugs.

Reinvigorating antimicrobial R&D and facilitating equitable global access to antimicrobials are two sides of the same coin. If R&D incentives are a collective global responsibility — as the pharmaceutical industry and some high-income member states have argued in the context of High-Level Meeting declaration negotiations — so too is ensuring that new drugs meet the most pressing public health needs.

Pull incentives that are currently on the table — notably the PASTEUR Act proposed in the US and transferable exclusivity vouchers (TEVs) in the EU — fail in this regard. Even as they offer handsome rewards to drug developers, they leave all decisions regarding pricing, manufacturing, distribution, and follow-on research to entities with no public-health mandate and a responsibility only to deliver returns to shareholders. They also do nothing to facilitate the scientific collaboration and follow-through that is badly needed to overcome persistent barriers in antimicrobial development and inform appropriate use.

Alternatives to proposed pull incentives

As an alternative, public health research authorities and non-profits like GARDP are well-placed to play a much more active role in antimicrobial R&D and make responsible, public-health-centered decisions regarding the pricing, production, and distribution of resulting products — with no conflict between their mandate and the goals of stewardship and access. Indeed, public and non-profit drug developers by their nature most fully enact the “delinkage” of R&D incentives from sales volumes and prices called for in the declaration agreed to by member states at the last High-Level Meeting on AMR in 2016.

Such initiatives are also more cost-effective and therefore a more prudent use of public resources. They also have a strong track record of research collaboration, for example through global clinical trial networks, and success in getting products from discovery to delivery: the US government, for example, already plays a significant and underappreciated role in late-stage drug development, and the non-profit Drugs for Neglected Diseases initiative (DNDi) has brought 13 treatments to market for 6 neglected tropical diseases since 2003. Through the SECURE Antibiotic Facility collaboration with WHO, GARDP is also actively developing feasible and effective approaches for strengthening antimicrobial stewardship in lockstep with introduction of new drugs.

Governments should commit not only to prioritize public and non-profit R&D initiatives when channeling public funds, but to structure all pull incentives that aim to bring new antimicrobials to market in ways that encourage timely, equitable, and affordable access to resulting drugs in the places they are needed most. This entails attaching certain terms and conditions, including provisions demanding that developers and manufacturers: are transparent about clinical trials, R&D costs and product prices; register their products in LMICs within a short, fixed timeframe; price their products affordably; promote diversified manufacturing; engage with non-profit and multilateral initiatives focused on facilitating access for LMICs; conduct post-approval research on highly impacted patient groups; and establish and participate in large global clinical trials with sites in LMICs in order to generate much-needed evidence about whether and how these drugs work for patients who are most affected by AMR.

Finally, political leaders must also remember that new antimicrobials are just one part of the solution. R&D is also needed for new diagnostic tools and the global AMR response, more broadly, is glaringly underfunded: not all countries have yet formulated national action plans to counter AMR, and among those that have, only one in five has identified funding to finance their implementation. MSF has witnessed first-hand the dire needs for improved infection prevention and control, antimicrobial stewardship, and microbiological laboratory capacity in many communities where we work. No quantity of new antimicrobials will stem the tide of AMR in any country if these gaps in access to quality health care are not filled in all countries.

Access to quality care, including lifesaving antimicrobials, should not be a luxury if we want to save patients — and modern medical care as we know it — from the acute and growing crisis of AMR.

This piece was originally published by Geneva Health Files on 23 July 2024

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This blog by the MSF Access Campaign reflects on our experiences advocating for global equitable access to medicines, vaccines and tests. msfaccess.org