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. Two recent studies found that the virus that causes COVID-19 is developing resistance to two antiviral drugs commonly used for treatment in patients with compromised immune systems: remdesivir and nirmatrelvir. The first study from Cornell University and US National Institutes of Health researchers, which specifically looked at immunocompromised patients, found that the virus developed a reduced sensitivity to the drugs, while the second study from University of Pittsburgh, Brigham and Women’s Hospital, Stanford University, and Harvard University researchers also found resistant mutations, with the effect more evident in the immunocompromised and those who had received nirmatrelvir. These results raise concerns as the threat of antimicrobial resistance globally grows.Researchers from the University of California, Riverside; the University of California, Irvine; and the Yale School of Medicine have designed a new synthetic compound, MED6-189, which is effective against drug-sensitive and drug-resistant Plasmodium falciparum malaria strains in vitro and in mice engineered to have human blood. MED6-189, inspired by a compound extracted from marine sponges, works by targeting and disrupting a specialized part of P. falciparum cells, as well as the pathways used to transport materials within the cells, thereby preventing the pathogen from developing resistance. The next steps include continued optimization of the MED6-189 and further confirmation of its mechanisms of action, but, if the compound continues to demonstrate success, this research could lead to the development of an important tool to address the rising challenge of antimalarial drug resistance.Last week, the US Department of Health and Human Services through the Advanced Research Projects Agency for Health announced funding for the Transforming Antibiotic R&D with Generative AI to stop Emerging Threats project that will use artificial intelligence (AI) to speed up the discovery and development of new classes of antibiotics to meet the urgent need for new drugs amid the growing threat of antibiotic resistance. While conventional antibiotic discovery methods require time-consuming manual screening and testing of potential molecular compounds, most of which do not advance into further development, this project will employ deep learning to develop new methods to identify biomolecules with potential and use generative AI to expand the number of potential antibiotic candidates.

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 Biomedical Advanced Research and Development Authority (BARDA) has awarded an agreement worth up to $268 million over 12 years to Swiss company Basilea Pharmaceutica to support the development of novel, first-in-class antifungals and antibacterials in its portfolio. The initial funding will specifically serve the further development of fosmanogepix, which is expected to enter soon a Phase 3 trial for invasive yeast infections, and BAL2062, which has the potential to target the common mold Aspergillus and has most recently completed a Phase 1 safety study. The news comes as investment in new antimicrobials continues to wane and the threat of antimicrobial resistance continues to rise globally.A recent study found that the protection offered by the Jynneos mpox vaccine greatly wanes 6 to 12 months after vaccination, raising concerns about the need for booster doses and the potential of breakthrough infections among vaccinated people amid the ongoing global mpox emergency fueled by the severe clade 1b of the virus. The Jynneos vaccine is meant to be given as two doses a month apart, but to offer protection to more people and to conserve a limited supply of doses, many were offered just one dose early on in the 2022 clade 2 mpox outbreak. The study found that after one year, the antibody levels in participants who had two doses were comparable or lower than the peak antibody responses in people who had received only one.The US National Institutes of Health (NIH) recently announced a new network that will research pathogens that currently lack effective treatments and vaccines to identify strategies to develop safe and effective medical countermeasures before a new pandemic threat arises. The network, which comes in the wake of the COVID-19 pandemic and the midst of ongoing emerging infectious disease outbreaks, will focus on developing tools that target viral families that are known to cause human disease, such as the families that include dengue and yellow fever, measles, polio, and chikungunya. The agency’s National Institute of Allergy and Infectious Diseases has committed up to $100 million annually to the network.

It has been nearly eight years since antimicrobial resistance (AMR) gained political attention at the highest levels. At the United Nations (UN) High-Level Meeting (HLM) on AMR in 2016, countries vowed to take a coordinated approach to address the root causes of AMR. Now, close to a decade later, progress has been uneven at best. While many countries have tried to tackle the issue by developing their own national action plans, fewer than a fifth of these plans are funded or implemented. And while annual global funding for antibiotic research and development (R&D) increased by 25 percent since 2017, access remains a challenge, as many new antibiotics never get registered and remain unaffordable in low- and middle-income countries (LMICs).On September 26, the UN is hosting a second HLM, aimed at accelerating multisectoral global, regional, and national action to address AMR. Will this be the moment where key global decision-makers generate lasting political momentum to make meaningful progress addressing this silent pandemic?Renewed sense of urgency to address AMR and invest in R&DThe upcoming meeting will occur amid a sense of renewed urgency around addressing AMR. A recent Lancet report highlights that drug-resistant pathogens could cause more than 39 million deaths over the next 25 years, forecasting that AMR deaths will increase steadily in the coming decades if remediation measures are not in place.A study by the Global Research on Antimicrobial Resistance Project predicts that AMR mortality will increase by 70 percent by 2050 and notes that the most impactful way to prevent this outcome is through improving access to effective antibiotics, particularly in LMICs, where the burden of disease continues to be the greatest. The study also suggests that the traditional model of drug development may not be sustainable for antibiotics, as most new products never reach key populations in LMICs because they are not able to overcome regulatory challenges and remain too expensive. Unless access and affordability are assured, the global mortality burden from resistant bacterial infections will continue unabated. Ensuring there are political commitments to strengthen the AMR R&D ecosystem will be crucial in realizing progress.2024: The year of AMR?The good news is that, in many ways, 2024 has already been the year of AMR. In May, the World Health Organization (WHO) delegates approved a resolution to accelerate national and global responses on AMR, with many of them highlighting it as a crucial building block for the HLM this fall.The resolution welcomes WHO’s strategic and operational priorities to address drug-resistant bacterial infections in the human health sector, including strengthening R&D to support the creation of new tools to combat AMR and replenish the shockingly waning pipeline.AMR has also continued to feature in G7 and G20 discussions, and member states are largely expected to include provisions focused on combating the silent pandemic in political outcome documents later this fall, including recognizing the need for new investments in research and greater support to initiatives like the Global AMR R&D Hub.Political declaration: Commitments on a path forwardSo, what constitutes success for the HLM on AMR? Much of it comes down to the commitments and pledges made in the political declaration that will be adopted by delegates. The good news is that the final draft includes some strong targets, including one to reduce global deaths from bacterial AMR by ten percent by 2030. Countries are also pledging to develop their national action plans by 2030, of which 60 percent would need to be adequately funded by the deadline (compared to the roughly 20 percent which are to date).Perhaps most notable though is the request for the Quadripartite—which is comprised of WHO, the World Organization for Animal Health, the UN Food and Agriculture Organization, and the UN Environment Programme—to establish an Independent Panel on Evidence for Action. The panel would serve a key function by supporting member states’ decision-making with regular guidance on the trends of science, data, and evidence across AMR-related sectors.R&D is also a central pillar in the declaration, with member states recognizing the need for increased public-health-driven R&D and the role of public-private partnerships like the Global Antibiotic Research & Development Partnership and the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator. The text encourages the use of push and pull incentives to spur R&D while ensuring mechanisms are in place for equitable access. Countries are called upon to develop and incentivize the adoption of manufacturing standards, promote the transfer of technology and know-how, encourage research, and undertake measures to address the growing shortage of researchers and medical specialists.It is worth celebrating the inclusion of several numeric targets, as many past political outcome documents coming out of UN health-focused high-level meetings did not feature such specific and explicit provisions and pledges. However, while the political declaration offers a good framework for making bigger shifts in the fight against the silent pandemic and ensuring a more explicit focus on equitable access to health technologies to fight AMR, additional funding and research targets would have led to an even stronger outcome, as targets lead to better transparency and accountability.What’s next?Member states are largely expected to adopt the political declaration on Thursday without much controversy. The question is: what’s next? There will certainly be opportunities to further advance the work on AMR in other forums, such as the G7 and G20, as well as at the AMR ministerial in Saudi Arabia in November. The AMR political declaration includes a commitment by countries to raise $100 million to aid implementation of national action plans, and follow-through on the principles and targets will be key in the months (and years) ahead, especially with the next AMR meeting not scheduled until 2029. The 79th UN General Assembly will be a pivotal moment to garner the high-level political commitment needed to ensure sustained focus on the ongoing challenges around AMR and to shift from dialogue to action to combat the silent pandemic.

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. A research team from Brazil has identified a potential target for a novel therapeutic to combat infections caused by Aspergillus fumigatus, a fungal species that, alongside other Aspergillus fungi, can cause potentially fatal complications in patients with weakened immune systems and is listed by the World Health Organization as a priority fungal pathogen. The researchers are now working to find a molecule that can inactivate the target identified by the research and potentially serve as the basis for a novel drug to target the fungus. This discovery comes in the face of rising resistance to existing antifungals, an absence of newly approved ones in recent years, and often unpleasant side effects that can accompany those that are currently available. A recently published study found that Moderna’s mRNA vaccine candidate was better than the currently available Jynneos vaccine at preventing severe mpox and reducing virus levels in monkeys. Moderna started advancing preclinical development for an mpox vaccine candidate during the last declared public health emergency of international concern for the virus in 2022. The candidate, mRNA-1769, contains mRNA molecules that code for four proteins on the surface of the mpox virus that are vital for viral replication and that are shared by other orthodox viruses. The candidate was able to neutralize other orthopox viruses, including camelpox, rabbitpox, and multiple mpox strains, in lab tests, suggesting that the vaccine could provide broad protection against a range of orthopox viruses, as well as offer a potentially safer, more effective, and easier- and quicker-to-manufacture alternative for mpox. A multi-institution research team discovered and isolated a broadly neutralizing antibody that could form the basis of a future treatment for current and future variants of the rapidly mutating virus that causes COVID-19. The researchers isolated a plasma antibody from a single patient that was broadly neutralizing—or able to neutralize all known variants of SARS-CoV-2, the virus that causes COVID-19, as well as distantly related SARS-like coronaviruses that infect other animals—and then obtained the exact molecular sequences of the antibody in the hopes of being able to manufacture it as a future treatment, as well as enable research toward a universal vaccine. This discovery provides some hope as cases of COVID-19 spike once again.