A partnership that could help expand access to new antibiotics in low- and middle-income countries (LMICs) was announced yesterday.
The agreement between the Global Antibiotic Research and Development Partnership (GARDP) and the Stop TB Partnership's Global Drug Facility (GDF) aims to address one of the critical issues that has emerged in the fight against antimicrobial resistance (AMR): Many of the low-resource countries that are being hit hardest by increasingly drug-resistant infections have limited or no access to the small number of new antibiotics that could treat those infections. And even when those drugs are available in those countries, they're largely unaffordable.
GARDP and GDF officials say that by pooling procurement of antibiotics in the GARDP portfolio and using the platform that GDF has developed to get tuberculosis (TB) drugs and diagnostics to millions of TB patients, the partnership is taking a step toward building a globally coordinated system for getting new antibiotics to the countries where most of the deaths from drug-resistant pathogens are occurring.
"This partnership is a major step toward placing equity at the heart of the international response to AMR," Manica Balasegaram, MRCP, MSc, executive director of GARDP, said in a press release. "By positioning AMR, like tuberculosis, as a public health issue to be prioritized, we can build an ecosystem for appropriate access to antibiotics for patients around the world."
An 'ecosystem' for wider antibiotic access
GDF Chief Brenda Waning, PhD, MPH, said the hope is that this agreement could be a building block for an ecosystem akin to the one that has helped get drugs for HIV, TB, and malaria developed and distributed to millions of patients around the world.
"There have been substantial investments in the big three diseases that have created a whole ecosystem that encourages R&D [research and development], encourages development of drugs, and all of the things that need to happen to get them where they need to be," Waning told CIDRAP News. "But AMR lags far behind. That ecosystem does not exist."
The first test-case for the partnership will be cefiderocol, an antibiotic that targets multidrug-resistant infections with limited or no treatment options. Like many new antibiotics, cefiderocol is currently commercialized only in the United States and a handful of European countries. But in 2022, under a license and technology transfer agreement with drug developer Shionogi and the Clinton Health Initiative, GARDP obtained the rights to manufacture and commercialize cefiderocol in 135 LMICs.
The partnership with GDF, which was created by StopTB Partnership in 2001 to promote equitable access to TB drugs and diagnostics, will help GARDP take the next step toward making this a reality. Working with the World Health Organization (WHO), GARDP will identify the countries in which cefiderocol is most needed and where barriers to access exist, implement plans to get the drug registered and commercialized in those countries, and help develop guidelines for appropriate use. GDF, using the tools it's developed over 20 years to facilitate wider access to TB drugs, will help with budgeting, ordering, and supply chain management.
By positioning AMR, like tuberculosis, as a public health issue to be prioritized, we can build an ecosystem for appropriate access to antibiotics for patients around the world.
The model will also be used to expand access to zoliflodacin, an oral antibiotic for gonorrhea that could be approved within the next year. GARDP is working with Innoviva Specialty Therapeutics to conduct phase 3 trials for the drug and has acquired the rights to register and commercialize it in 168 countries upon approval.
Waning said the idea is to create a coordinated, "end-to-end" approach that addresses barriers to antibiotic access at every stage.
"GARDP is really working on the front end, and then we come in and say, 'Now we can help get rid of some of the barriers and get the products into those countries,' " she said.
More partnerships needed
Much of the focus in recent years has been on the weak antibiotic pipeline, which experts say is failing to keep pace with rising rates of AMR. Compared with other drugs, relatively few new antibiotics have been approved over the past two decades, and few of them are the type of novel antibiotics needed for the difficult-to-treat infections caused by organisms on the WHO's priority pathogens list.
But even when these drugs are approved, they're largely unavailable in LMICs. This issue was highlighted in a 2018 study published in PLOS One. The study found that, of the 25 new antibiotics that entered the market from 1999 to 2014, only 12 were registered in more than 10 countries.
"Overuse of antibiotics is often addressed as one of the main reasons for development of antibiotic resistance," the study authors wrote. "Lack of availability, and therefore access, is however equally problematic since this has been shown to lead to increased use of inappropriate treatments."
Progress on this issue has been slow. A report last week from the Access to Medicine Foundation found that the companies developing four innovative new antibiotics that could soon be on the market—and one that's recently been approved—have not used all the tools at their disposal to ensure that that their products will be available in LMICs. Among the findings was that, for all five products, concrete commitments for registration were only identified in five LMICs.
There have been substantial investments in the big three diseases that have created a whole ecosystem that encourages R&D [research and development], encourages development of drugs, and all of the things that need to happen to get them where they need to be....But AMR lags far behind. That ecosystem does not exist.
That's why an author of that report, Access to Medicine Foundation director of operations and research Marijn Verhoef, PharmD, is encouraged by the GARDP-GDP partnership.
"In order to ensure sustainable access to antibiotics for patients worldwide, partnerships and tailored approaches are necessary, especially for low- and middle-income countries, Verhoef said in an email. "We need more of these critical partners to work together to curb AMR."
Waning said the current ecosystem for antibiotic access is similar to what existed for HIV, TB, and malaria drugs in back in 2000. And while she believes the partnership with GARDP is a good starting point, she says more stakeholders, and more funding, will be needed to create the kind of infrastructure that has substantially expanded access to HIV, TB, and malaria drugs over the past two decades.
"I'm hoping that with this growing interest in AMR, and with the [United Nations] high-level meeting, that there'll be some serious resources put toward building what is needed to replicate that kind of success," she said. "Because you'll need a lot more than us."
