Breakthroughs Blog: Mpox

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 new study found that LC16m8, an attenuated vaccinia virus strain originally developed in Japan for smallpox and later approved for mpox in 2022, induced strong responses and was safe in mice, monkeys, and healthy adult humans, potentially paving the way for the development of broadly effective mpox vaccines. The researchers vaccinated mice with LC16m8 to see how it protected them from mpox, later vaccinating monkeys and healthy adult volunteers as well to study their blood samples for immune responses and monitor them for safety. The results underscore LC16m8’s potential as a safe, effective, and scalable choice for mpox vaccination and also provide a blueprint for developing next-generation vaccines against other poxviruses and emerging pathogens.Researchers from Abertay University and Bangor University have developed a prototype blood test that can detect up to five infections at the point of care, providing results quickly via a smartphone app. The tool, which was piloted using tuberculosis as a test case, showed high sensitivity and an ability to accurately identify cases. The speed and convenience, as well as the much lower cost compared to lab testing, demonstrate the test’s potential to be a game changer in ensuring access to timely testing and diagnosis, particularly in remote locations and other settings lacking laboratory infrastructure.  The results of a Phase 3 clinical trial published last week found that Moderna’s combination COVID and flu shot outperformed existing individual vaccines for both viruses. The combination shot uses the same mRNA technology as Moderna’s approved vaccine for COVID-19, but there are no currently approved mRNA flu vaccines. In a trial that included more than 8,000 adults, the combination vaccines generated higher antibody levels for COVID and all but one influenza strain in trial participants who got the combination vaccine compared to those who got individual vaccines. A combination vaccine could help boost vaccination levels for both viruses, and an mRNA vaccine, in particular, could also speed up production because they are faster to make than current flu shots.

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 new study led by a multi-country research team has found that the Xpert MTB/Ultra molecular diagnostic test for stool samples, which is currently only recommended for tuberculosis (TB) diagnosis in children, could serve as an alternative TB diagnosis option for adults living with HIV—a potential gamechanger for improving diagnosis among this population. Thirteen percent of the 1.25 million TB deaths in 2012 were among people living with HIV, but access to the sputum- and urine-based tests currently recommended for TB diagnosis in this population is limited in many settings, and they are not effective for all people living with HIV. The researchers found that, compared to current tests, the stool test was effective, and, in some cases, even identified additional cases that were not detected in sputum or bacterial culture.The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) last week announced a $3.7 million award to ArrePath to support its first-in-class antibiotic for treating complicated urinary tract infections caused by multidrug-resistant Enterobacterales bacteria. If it proves successful, the novel antibiotic class could target the vast majority of multidrug-resistant Enterobacterales infections. The class of antibiotics also has attributes that suggest it could be administered orally or intravenously, allowing more flexibility for patients. ArrePath identified the new class using an artificial intelligence and machine-learning-enabled approach.Last week, the US Food and Drug Administration approved a freeze-dried formulation of Bavarian Nordic’s vaccine for mpox and smallpox, Jynneos, enabling additional flexibility in stockpiling doses of the vaccine to prepare for future outbreaks of smallpox or mpox. The freeze-dried vaccines are easier to store and transport and have a longer shelf life than the frozen liquid version, which was approved in 2019. Bavarian Nordic will deliver the first freeze-dried vaccines later this year.

In many ways, 2024 has been a year marked by change—the first new year since the official end of the COVID-19 pandemic and a record number of elections ushering in political transitions around the world. With the global spotlight shifting to antimicrobial resistance (AMR) and tuberculosis (TB) reclaiming the designation as the top infectious disease killer from COVID-19, it may seem, at first glance, that the world has moved on from the pandemic that dominated every aspect of life for the better part of four years. However, with a deeper look, it’s clear that the global community is still reacting to and learning from the pandemic—for better or worse.As the year comes to an end, GHTC is reflecting on the global health innovation news and policies that shaped 2024.1. New disease outbreaks arise around the world, spurring need for and progress in R&D.In 2024, disease outbreaks continued to dominate the headlines—from the first reports of avian flu in the United States in March to the rapid global spread of the clade 1b mpox strain over the summer to the outbreak of the deadly Marburg virus in Rwanda beginning in September. Each of these incidents exposed devastating gaps in our prevention and response toolkit and spurred important steps forward on research and development (R&D) and access.For example, in response to the worrisome spread of avian flu, both the World Health Organization (WHO) and the US government launched efforts to accelerate the development of mRNA vaccines that could be deployed in case of human-to-human transmission of the currently spreading strain of avian flu or redirected to target another form of pandemic influenza if needed. Additionally, following declarations from the Africa Centres for Disease Control and Prevention and WHO designating mpox a public health emergency this past August, WHO prequalified the first vaccine against mpox and approved the first mpox test for emergency use, with the goal of accelerating global access to these critically needed tools. The outbreak also provoked new research to develop improved vaccines against mpox and the broader range of orthopox viruses, with early studies of mRNA mpox vaccines in macaques and mice demonstrating promising results.This fall, as cases of Marburg were on the rise in Rwanda, and with no currently approved vaccines or treatments available, researchers fast-tracked efforts to evaluate tools to stem the current outbreak and curb future ones. Rwandan health authorities initiated an open label vaccine trial in health workers and others at heightened risk, and there has since been a randomized clinical trial arm launched, which will offer critical efficacy data. Additionally, scientists launched the first-ever clinical trial for a Marburg treatment this year.Beyond accelerating innovation against these outbreaks, 2024 also brought exciting research advancements targeting other pathogens scientists believe are most likely to cause the next pandemic, including trials that could lead to the first-ever approved vaccines for Sudan ebolavirus and Lassa fever, as well as further efforts to improve coronavirus vaccines and simplify and speed up vaccine development and manufacturing.2. Pandemic preparedness policy reforms march forward while post-COVID political backlash in United States grows.Multilateral efforts to strengthen the world’s pandemic preparedness and response architecture moved incrementally forward this year. At the World Health Assembly (WHA) in May, member states adopted several amendments to the International Health Regulations—an existing framework codifying international responsibilities during a pandemic—, including new commitments to solidarity and equity on financing and ensuring access to medical products. The World Bank-hosted Pandemic Fund, a financing mechanism launched in 2022 to help low- and middle-income countries strengthen their preparedness and response capacities, also raised $982 million in new contributions and an additional $1.8 billion in co-financing this year, as well as awarded $500 million in grants to countries to strengthen surveillance, laboratory, and workforce capacities and fast-tracked an additional $129 million for the mpox response. Under the Brazilian presidency, G20 nations established a voluntary coalition to strengthen local and regional production of health products, which, while focused foremost on neglected diseases, could also strengthen capacities critical for pandemic preparedness and response. Unfortunately, despite some progress on negotiations toward a new pandemic accord, countries failed to reach sufficient consensus before the end of this year, and negotiators are now pushing to wrap up by the next WHA in May of 2025.At the same time as some progress was achieved on the international front, in the United States, post-COVID political backlash has deepened and become more entrenched through congressional scrutiny and reform agendas targeting the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC). Though the fiscal year 2025 budget is not expected to be finalized until next year, the health-related spending bill introduced by the House proposes spending cuts to CDC and a reorganization of NIH, which mirrors that put forward by House Republicans over the summer and could have serious implications for the agency’s core global health R&D capacities. Beyond appropriations, we also continued to see a plethora of congressional hearings targeting NIH and CDC on the origins of COVID-19, gain-of-function research, China’s influence, and the perception that these agencies are overstepping their mandates. The scrutiny and reform efforts we saw this year are expected to intensify in 2025, as Republicans gain control of both chambers of Congress and the White House.3. AMR captures the world’s attention as the global threat continues to grow.2024 was informally dubbed “the year of AMR,” with AMR elevated on the global agenda at several key moments. In May, a WHA resolution was adopted to accelerate national and global responses to AMR by advancing R&D, strengthening surveillance systems, and forging international partnerships. Later in September, a landmark report found that without further policy interventions, the death toll from AMR is expected to reach 39 million between 2025 and 2050—the equivalent of three deaths per minute.This shocking report set the scene for the United Nations High-Level Meeting on AMR in September, which led to the adoption of a political declaration that set the goal to reduce AMR deaths by 10 percent by 2030 and committed countries to promote the R&D of and equitable access to antimicrobials, vaccines, diagnostics, and other products. Global leaders also adopted an action plan in November, built off of the declaration, to provide actionable objectives and additional check-ins to monitor progress.This political momentum on AMR was also matched by exciting research breakthroughs that made the news this year. Researchers discovered a new compound that could potentially treat a resistant bacterial pathogen that can cause lethal hospital infections. Additionally, Phase 3 trials yielded promising results for both a therapeutic option for patients with serious bacterial infections and limited treatment options, as well as a new antibiotic that could cure uncomplicated gonorrhea infections, which could be approved sometime next year.4. TB reclaims title of deadliest infectious disease, but promising trials offer hope. This past year, TB surpassed COVID-19 to reclaim the spot as the world’s leading infectious disease killer, according to WHO’s Global Tuberculosis Report 2024. While this sobering news underscored major gaps in the tools needed to prevent, diagnose, and treat TB, especially drug-resistant TB, 2024 also brought exciting news on the research front that will hopefully help fill them.In March, a Phase 3 trial launched in South Africa, which is testing a TB vaccine candidate that could eventually become the first vaccine to prevent pulmonary TB in adolescents and adults. The only approved TB vaccine on the market, which was developed more than 100 years ago, is effective at preventing some types of TB in infants, but it offers inconsistent protection in adults against pulmonary TB. Additionally in November, the endTB consortium announced the completion of the first Phase 3 randomized controlled trial to exclusively enroll people with pre-extensively drug-resistant TB, a very hard-to-treat form of TB. Preliminary results demonstrated that a shorter, less toxic treatment strategy achieved high cure rates. Earlier in the year, WHO also recommended three new regimens for multidrug- or rifampicin-resistant TB, offering a much-needed variety of therapeutic alternatives for those with multidrug-resistant TB. 5. A major HIV breakthrough, but work remains on access. In what has been hailed as a breakthrough in HIV prevention, in 2024, exciting results were reported from a series of clinical trials for Gilead’s long-acting HIV prevention drug, lenacapavir, which found that the drug was 100 percent effective in preventing HIV in cisgender women and adolescent girls and 96 percent effective among cisgender men, transgender men and women, and gender nonbinary individuals who have sex with men. Both trials were so successful that they were unblinded early to offer the drug to all participants. Lenacapavir, which is administered via a twice-yearly injection, is currently approved as a treatment for multidrug-resistant HIV, but, if approved as a preventative regimen, the drug could be a game-changer for the HIV pandemic.Advocates applauded Gilead for its historic commitment to inclusion in these trials, while also urging that lenacapavir be made accessible and affordable as soon as possible to those that most need it. In October, Gilead announced a plan to allow generic versions of the drug to be sold in 120 countries, including all those with the highest HIV rates. However, the plan faced criticism for excluding most middle- and high-income countries that account for around 20 percent of new HIV infections. In these countries, the originator drug will only be available at higher prices, making it potentially inaccessible to at-risk populations.In other welcome HIV prevention news, in October, Population Council announced the results of a Phase 1 trial, which suggest that a three-month dapivirine vaginal ring for HIV prevention will be as effective as the currently approved one-month ring. The ring, which is self-inserted into the vagina and slowly releases an antiretroviral drug to prevent infection over three months, was found to deliver the drug at higher levels than the one-month ring. If the longer-acting ring continues to demonstrate success, it could offer a more cost-effective and convenient option for at-risk women. 6. Trump presidency and Republican trifecta portend changes to US leadership in global health.In the November election in the United States, former President Donald Trump won the presidency and Republicans gained control of both the US House of Representatives and the Senate. It was an across-the-board victory that will portend changes to US leadership on global health and medical research. If past is prologue, we’re likely to see President-elect Trump once again propose significant funding cuts to US global health programs and public health agencies like NIH and CDC, as well as withdraw the United States from WHO and other multilateral initiatives, the latter of which could derail efforts to finalize a pandemic accord. Given that the United States is the largest funder of global health programs and global health R&D efforts, these political changes could have a reverberating impact on health around the world.Since winning the presidency, President-elect Trump has also nominated several controversial picks to lead America’s public health agencies. These include Robert F. Kennedy Jr, a noted vaccine skeptic who has expressed a desire to cut the NIH workforce and refocus the agency on chronic diseases over infectious diseases, to lead the Department of Health and Human Services; Dr. Jay Bhattacharya, a health economist who criticized public health measures during the COVID-19 response and a vocal critic of NIH, to lead NIH; and Dr. Dave Weldon, a former Congressman who has questioned vaccine safety, to lead CDC.On the congressional front, with Republicans now in control of both chambers of the US Congress, as discussed, we’ll likely see continued scrutiny and reform efforts targeting NIH and CDC, as well as potential spending cuts to health and foreign assistance programs.7. New policies and innovative research approaches help reach underserved populations.Every person, everywhere, deserves to benefit from the fruits of science, and in this otherwise tumultuous year, there were several successful efforts to advance more inclusive clinical studies. In September, WHO released new guidance on clinical trial best practices outlining practical considerations for trials to include children and pregnant and lactating individuals, populations currently underrepresented in trials, leading to a lack of approved technologies for these groups. This guidance aligned with WHO’s living toolkit to facilitate the inclusion of pregnant and breastfeeding populations in clinical trials that was published earlier in the year. 2024 also brought the launch of two historic trials that aim to diversify research and thereby ensure that future technologies will serve the needs of underserved populations. This summer, a global consortium launched the first-ever Phase 3 clinical trial testing the efficacy and safety of antimalarials in women in their first trimester of pregnancy, which will hopefully not only lead to an urgently needed new treatment option for these women but also set a precedent for the inclusion of pregnant women in future clinical trials. Earlier this year, the US Administration for Strategic Preparedness and Response also announced funding to Walgreens to support a decentralized clinical trial testing COVID-19 vaccines. This unique approach will allow for a more diverse pool of study participants by bringing the study closer to where they live, ultimately ensuring that the resulting data reflects real-world use among a broader swath of the population. In the end, 2024 proved to be a complicated year, marked by both scientific and political steps forward and back. As new innovations and policies emerge in 2025 and beyond, GHTC will continue to work to ensure support for global health R&D remains a political priority and that the gains we have already made on neglected and emerging health challenges are not only sustained but also strengthened to combat an evolving health landscape.For other fascinating global health news delivered to your inbox weekly and to stay abreast of developments in 2025 and beyond, sign up now to receive GHTC’s R&D News Roundup newsletter.

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. Last week, Detect Diagnostics announced that it received approximately $5.9 million in grants from the Bill & Melinda Gates Foundation to support further development of the company’s infrared light-based point-of-care system and assays to detect protein biomarkers of infectious disease. The Visualization by Infrared PEptide Reaction (or VIPER) diagnostic technology can detect bacteria, viruses, and fungi directly from samples and is simple to use, fast, low-cost, sensitive, and portable, making it suitable for low- and middle-income countries, which face a high burden of infectious disease. The grants include specific funding to advance the development of a test to detect tuberculosis.Last week, the National Institute of Allergy and Infectious Diseases and Siga Technologies announced that patients are no longer being enrolled in a clinical trial testing the antiviral drug tecovirimat (or Tpoxx) as a treatment for mpox. The study’s Data Safety and Monitoring Board recommended cessation after the drug did not hasten lesion healing or pain relief in adults with mild to moderate clade 2 mpox at low risk for severe illness, and an additional assessment showed a less than 1 percent chance that the study would demonstrate efficacy if enrollment and follow-up were completed. This news comes amid the ongoing global outbreak of clade 1 mpox and following the 2022 global outbreak of clade 2 mpox. While this trial and another testing Tpoxx for mpox did not show that the drug helped to accelerate lesion healing, before 2022, no treatment candidate had been studied in people with mpox, and this research represents an important step in the ongoing work of finding tools to address mpox.A recently published study introduces a proof-of-concept for a novel class of antivirals targeting a type of enzyme essential to several families of viruses—which include several pathogens that scientists believe are most likely to cause the next pandemic—, potentially paving the way for a faster and more robust response to future outbreaks. The research team screened hundreds of thousands of compounds, using the ones they discovered to create an optimized drug candidate that was then tested in mice, finding that the candidate could treat COVID-19 on par with Paxlovid, remain effective even if the virus mutated, and cause minimal side effects. The researchers say they need an industry partner before they can test the compound in humans, but they are working on developing compounds that could target other priority viruses that share the targeted enzyme, including RNA viruses like Ebola and dengue, as well as cytosolic-replicating DNA viruses like mpox.