Breakthroughs Blog: Antimicrobial resistance

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. The World Health Organization (WHO) last week announced its first COVID-19 vaccine license agreement through the COVID-19 Technology Access Pool (C-TAP) with Taiwanese manufacturer Medigen Vaccine Biologics Corp. The vaccine license was acquired through the Medicines Patent Pool, which also enabled last week additional agreements under C-TAP for a COVID-19 vaccine prototype and a test used to measure COVID-19 antibody levels. While C-TAP was launched at the height of the pandemic to promote technology sharing to improve access, particularly to vaccines, in low-income countries, major pharmaceutical companies have thus far declined to join the initiative.A clinical trial led by researchers at St George’s, University of London found that a higher dose of the antibiotic rifampicin for an abbreviated four-month treatment regimen for tuberculous (TB) was safe with no increases in side effects or toxicities, compared to the standard six months, which is WHO-recommended. The trial took place among adults with newly diagnosed pulmonary tuberculosis in Uganda, Guinea, Peru, Nepal, Botswana, and Pakistan. Experts say shorter treatment regimens will help lower costs and increase patient compliance, which will in turn reduce transmission and the development of resistance to available TB drugs. CSL Sequiris announced that it received an award from the Biomedical Advanced Research and Development Authority (BARDA) to deliver a vaccine for bird flu to the US government, increasing BARDA’s stockpile in case of an outbreak. The company will deliver one bulk lot of the H5N8 A/Astrakhan antigen to the US government, whose development has been supported by BARDA in recent years. The agreement is intended to improve US national vaccine preparedness and is especially significant as bird flu continues to be detected around the world, including a small number of human cases.

The health ministers of G20 nations concluded their annual meeting last weekend with the adoption of an “outcome document” that includes welcome commitments to advance the research and development (R&D) of health products. While normally such a ministerial-level meeting would end with the release of a formal consensus communique, broader geopolitics derailed this process, with Russia and China opposing the inclusion of language condemning the Russian war of aggression against Ukraine. Below we break down what R&D commitments are included in the outcome document, why it matters, and where conversations are expected to go from here. What’s in the declaration? At the highest level, G20 nations made commitments to strengthen the global health architecture and “build more resilient, equitable, sustainable and inclusive health systems equipped to address ongoing global health challenges and future public health emergencies with equitable access to safe, effective, quality-assured and affordable vaccines, therapeutics, diagnostics, and other medical countermeasures.” They also reaffirmed their commitment to ending the epidemics of AIDS, tuberculosis, and malaria; achieving polio eradication; advancing universal health coverage (UHC) and the Sustainable Development Goals (SDGs); and tackling antimicrobial resistance (AMR). On the latter issue of AMR, the ministers vowed to strengthen R&D for AMR and further the development of novel antimicrobials. They welcomed the work of various international initiatives and GHTC members including the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) and the Global Antibiotic Research and Development Partnership (GARDP) and voiced continued support for the Global AMR R&D Hub, which was established under the German G20 presidency to promote AMR R&D coordination. On the broader issue of R&D for pandemic prevention, preparedness, and response (PPPR), G20 leaders agreed to support a World Health Organization (WHO)-led consultative process to develop an interim (and potentially later permanent) medical countermeasures (MCMs) mechanism to coordinate the end-to-end R&D, manufacturing, procurement, and equitable delivery of MCMs during health emergencies. They advised that such a mechanism should consider a “network of networks” approach, building off existing international and regional partnerships, and should be coherent with the outcomes of ongoing efforts to amend the International Health Regulations (IHR) and advance a binding pandemic instrument. Additionally, the ministers underscored the need to strengthen local and regional R&D networks and manufacturing capabilities, especially in low- and middle-income countries, as well as voiced support for what many call the “100 Days Mission” to develop and make available safe and effective vaccines, therapeutics, and diagnostics within 100 days of the identification of a pandemic or epidemic threat. They also noted the importance of public-private R&D partnerships—calling out the contributions of GHTC members the Coalition for Epidemic Preparedness Innovations (CEPI), Medicines Patent Pool (MPP), and FIND—and technology transfer and knowledge sharing “on voluntary and mutually agreed terms.”Why it matters?  G20 nations currently conduct and fund the majority of the world’s health R&D. Thus, it is great to see G20 leaders reaffirm the importance of R&D to achieving UHC, SDGs, and PPPR and demonstrate political will to accelerate R&D efforts. However, the outcome document is short on specifics as to how G20 countries intend to operationalize their many promises, and it disappointingly includes no new funding targets or commitments.  Additionally, going into this year’s G20 cycle, many observers and health advocates also expected that the G20 under the Indian presidency would play a more active role in envisioning and detailing a specific proposal for the creation of an end-to-end MCMs mechanism or platform to succeed and build upon the Access to COVID-19 Tools Accelerator. Instead, the G20 simply promised to support a WHO-led consultative process to design an interim mechanism and punted it to the International Negotiating Body (INB) process for a pandemic instrument to determine the prospects for a permanent MCMs platform. What’s next? With G20 nations offering few specifics on a vision to reimagine the global health architecture and advance an MCMs platform, the focal point for change is now squarely within the separate but interrelated processes now underway to amend the IHR, advance a pandemic accord that will create a more comprehensive framework for how countries will prevent and respond to outbreaks, and design an interim MCMs platform. While these processes have been ongoing, the deliberations have been stymied as countries struggle to reach consensus around thorny R&D topics like access and benefit sharing, with some pushing for more aggressive legally binding commitments for transparency, conditions on public R&D funding, patent waivers, and new supply chain mechanisms for ensuring low- and middle-income countries access to medical countermeasures. Questions remain on the full scope of some of the processes, and how they will delineate which issues will be tackled where and with the target date of May 2024 for the adoption of an instrument rapidly approaching and the INB and IHR processes largely behind schedule, it remains to be seen what tangible changes for R&D can be realized. While it is impossible to know what exactly what the future of these negotiations hold, GHTC promises to continue to watch, weigh in, and report back in the months ahead as these interrelated processes unfold. Stay tuned! 

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. As COVID-19 infections and hospitalizations rise across the United States, last week Moderna reported initial data that showed the efficacy of their updated COVID-19 vaccine, which was originally aimed at protecting against the XBB.1.5 subvariant, against the increasingly dominant Eris (EG.5) and Fornax (FL 1.5.1) subvariants. The updated vaccine is expected to be available in the fall, pending approvals from US Food and Drug Administration (FDA) and other national regulators. Novavax, as well as Pfizer and partner BioNTech, are also advancing updated shots.The United Kingdom’s Fleming Fund last week announced that it will provide up to $267.5 million for strengthening antimicrobial resistance (AMR) surveillance capacity in low- and middle-income countries in Africa and Asia, where the threat and burden of AMR is the highest. Specifically, the funding will go to upgrading laboratories, introducing new genome sequencing technology, and supporting training sessions. This announcement, which came ahead of this past weekend’s G20 Health Minister’s Meeting, where AMR was an important topic, marks a significant investment in a data-driven approach to fighting the rising threat of AMR.A new antibiotic combination drug that could significantly improve the treatment of complicated urinary tract infections and potentially serious infectious caused by highly resistant bacteria is now on track to receive a final review by FDA. Cefepime-taniborbactam, developed by Venatorx Pharmaceuticals and the Global Antibiotic Research & Development Partnership (GARDP), could be approved as early as next February. If successful, the treatment would be the first new treatment in GARDP’s clinical development portfolio to gain regulatory approval and would be a boon to global equitable access to new antibiotic treatments due to GARDP’s exclusive rights to distribute and sub-distribute the treatment in 64 low- and middle-income countries.

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. Duke University researchers have developed a synthetic antibiotic, LPC-233, that could be effective against drug-resistant superbugs and bacteria. LPC-233 was found to be effective in protecting mice from fatal doses of multidrug-resistant bacteria by disrupting the synthesis of the outer membrane of the bacteria. LPC-233, which is a synthetic compound of the LpxC inhibitor, was developed after the first human trial of LpxC inhibitors failed because of cardiovascular toxicity. Hopefully, future studies will confirm the new antibiotic as a potential tool to address drug-resistant superbugs.Last week, the Project to Accelerate New Treatments for Tuberculosis (PAN-TB) collaboration announced the start of a phase 2b/c clinical trial to evaluate novel treatment regimens for drug-sensitive tuberculosis (TB). The trial, which is sponsored by the Bill & Melinda Gates Foundation, will evaluate two novel drug regimens made up of different combinations of five antibacterial agents—including the TB Alliance-developed pretomanid and the Janssen-developed bedaquiline— and will take place in high-burden countries starting with South Africa. The results will hopefully lead to a new, shorter pan-TB treatment regimen for patients.The Coalition for Epidemic Preparedness Innovations (CEPI) and Gennova Biopharmaceuticals last week announced a new agreement to advance the development of Gennova’s self-amplifying mRNA platform to create vaccine candidates against unknown pathogenic threats with pandemic potential. The funding will support the optimization and production of the platform technology and then the production of a vaccine candidate for preclinical studies against a known virus, rabies, to assess the new technology. This will hopefully lead to the development of novel RNA vaccines, which could offer significant advantages over existing mRNA vaccine platform technologies.