Breakthroughs Blog: Medicines

A new study sheds light on the findings of a recent trial evaluating the ability of a laboratory-made broadly neutralizing antibody (bnAb) to prevent HIV infection, pointing to approaches that could lead to more successful future antibodies and vaccines. bnAbs are naturally occurring antibodies that can neutralize multiple strains of HIV; they are considered a promising approach in HIV prevention research. A large, multicountry clinical trial evaluating a laboratory-made bnAb found that it did not significantly reduce overall HIV infections, although it showed some ability to reduce infections caused by highly sensitive strains. In the new study, researchers examined what happened in the participants who received the bnAb, discovering that there were extended periods of time when their antibody levels were too low to block less-sensitive strains of the virus. The study results suggest that more potent antibody concentrations and combinations of antibodies that attack the virus in different ways could have more success.An international research team has identified a crucial compound in the saliva of virus-carrying mosquitoes that could lead to a new prevention strategy for multiple mosquito-borne viruses. The researchers found that when mosquitoes infected with two orthoflaviviruses, West Nile virus and Zika virus, bite, their saliva contains not only the virus but also a viral compound that promotes infection by inhibiting the body’s initial immune response that is triggered when a virus enters the skin. The findings suggest that this viral compound could be shared among other orthoflaviviruses as well and could be a promising target for a preventive vaccine against multiple viruses from this group. The researchers have developed a vaccine targeting the compound that is now being optimized for clinical evaluation. New research from scientists in the United Kingdom highlights a new mechanism that a dangerous fungus uses to evade antifungal treatments. Candida auris is a priority pathogen that has caused outbreaks globally over the past two decades and can be highly fatal for vulnerable hospitalized patients. Current antifungal drugs work by targeting fungal cell walls, hindering the fungi from expanding. The researchers found that one way C. auris eluded treatment was by creating multiple versions of its entire genome, including a wide range of mutations in a specific gene that plays a key role in cell wall integrity. These findings point to new pathways for developing next-generation antifungals and combination antifungal regimens.

A study from the University of California, San Francisco found that a new long-acting HIV combination treatment could provide an alternative, more accessible option for some people with HIV. Long-acting treatment options can provide a simpler, more convenient alternative to daily pills for people living with HIV, but the only approved long-acting combination includes rilpivirine, which is not available in low- and middle-income countries, and the virus has been known to develop resistance to it and similar drugs. The new combination under study replaces rilpivirine with lenacapavir, which uses a different mechanism to target the virus. In the study, all participants achieved and maintained control of the virus. Additional clinical trials are planned to evaluate the approach more comprehensively, but, in the meantime, these findings could help guide care.  A team of researchers at the Massachusetts Institute of Technology has found a way to keep mRNA vaccines stable at higher temperatures, which could drastically lower costs and improve access to the technology in low-resource settings around the world. mRNA vaccines must be kept at extremely cold temperatures during transport and storage, requiring high costs and continuous monitoring. The researchers adjusted the formulation of the tiny particles that carry the mRNA, making them more resistant to heat. The vaccines the team produced can be stored at room temperature for up to a year or at nearly 100 degrees Fahrenheit for two months. Even after storage, the shots elicited equivalent immune responses in mice to the original formulations.The Medical Research Council/Uganda Virus Research Institute and the London School of Hygiene and Tropical Medicine have launched a Phase 1 clinical trial in Uganda evaluating the safety and immune response of a vaccine candidate for Bundibugyo, the severe strain of Ebolavirus behind the ongoing outbreak in the Democratic Republic of the Congo for which there are currently no licensed vaccines. Conducted in partnership with the Oxford Vaccine Group and Pandemic Science Institute at the University of Oxford, the trial builds on an ongoing Phase 1 trial of the same candidate in the United Kingdom. Both trials are funded by the Coalition for Epidemic Preparedness Innovations (CEPI). The candidate, ChAdOx BDBV, was developed by scientists at the University of Oxford and uses the same platform as the Oxford/AstraZeneca COVID-19 vaccine. 

Recently published results from a large multi-country study found that pooled tuberculosis (TB) testing could greatly reduce costs and boost access to diagnosis. Access to the gold standard of rapid molecular testing is limited—only just over half of people diagnosed with TB in 2024 were first tested using the technology. Instead, they were diagnosed using older technology, which can take weeks to produce results, during which the infection could progress or be transmitted to others. Millions of additional individuals with TB go completely undiagnosed. A major contributing challenge is that rapid molecular testing requires an expensive diagnostic cartridge for each sample. Pooled testing involves testing samples from multiple individuals with one cartridge. Patients are only retested individually if the result is positive. Unlike new diagnostic technologies, like AI-enabled portable X-ray machines, that are promising but would require additional funding to implement, pooled testing could be scaled up rapidly without new funding because it utilizes technologies that many labs already have.Medicines for Malaria Venture (MMV) is advancing the novel, first-in-class antimalarial compound, cabamiquine, into the next stage of clinical development, with the hope that the compound could be part of a single-dose, long-acting treatment for the prevention and treatment of malaria, which could greatly simplify care compared to current options. Cabamiquine was discovered by researchers at the University of Dundee, with financial and scientific support from MMV, and then advanced by Merck to proof of concept. Recently published results from two Phase 2a trials showed that a regimen of cabamiquine and pyronaridine was able to clear uncomplicated Plasmodium falciparum malaria in more than 90 percent of participants and demonstrated a strong safety profile. MMV will now lead Phase 2b clinical development of the compound. The Biomedical Advanced Research and Development Partnership (BARDA) recently announced that it has awarded Scynexis a $214 million contract for the development of an antifungal to treat and prevent invasive fungal infections, the less common but more serious form of fungal infection that penetrates deep into the tissues of the body. Fungal infections are a growing global challenge, but there is a significant gap in the pipeline of new tools to address them. Last year, the company reported positive findings from a Phase 1 trial of an oral dose of the candidate and is currently conducting a Phase 1 trial of an intravenous formulation. The award includes initial funding to advance the company’s antifungal candidate into Phase 2 trial, with an option for additional, longer-term funding. 

Recently published results from a Phase 2b trial testing a new regimen for people with chronic Trypanosoma cruzi infection could offer a safer, more practical treatment option for the infection, which affects more than seven million people globally, mainly in Latin America, and can develop into Chagas disease. Compared to the current standard regimen that involves twice-a-day treatment for 60 days and is frequently accompanied by uncomfortable side effects, leading to treatment failure, the new regimen involves a 30-day course taken once daily. Trial participants treated with the shorter regimen had significantly reduced side effects, found it easier to follow, and saw lower treatment interruption. If it continues to demonstrate success in large Phase 3 trials, the regimen could transform treatment for patients globally, as T. cruzi infection becomes a growing challenge in the United States, Europe, and Japan.The first participants have been vaccinated in a trial in the Democratic Republic of the Congo (DRC), where the country’s ongoing outbreak of the Bundibugyo strain of Ebola has now become the largest Ebola outbreak in the country’s history and the second largest in history. Health workers in Bunia, a DRC city at the center of the outbreak, were the first to be vaccinated in the real-world efficacy trial evaluating whether the Ervebo vaccine, which is designed to target the more common Zaire strain, offers some cross-protection against Bundibugyo. There are no approved vaccines for Bundibugyo Ebola, and there were no candidates in late-stage development before the start of the outbreak of the rarer strain of the virus, which has only caused three outbreaks since it was first discovered around 20 years ago. Since the outbreak began, global partners have fast-tracked the development of earlier-stage candidates, but researchers hope the Ervebo vaccine could provide some protection before those candidates are ready for evaluation in DRC. As artificial intelligence (AI) continues to rapidly transform many aspects of technology and science, including health research, a new report from the World Health Organization (WHO) speaks to how stakeholders can help ensure AI-enabled health research is conducted responsibly and benefits everyone. According to the report, while AI has the potential to accelerate health innovation and improve health outcomes, it also presents risks related to equity, privacy, safety, transparency, and more. WHO suggests that researchers, ethics committees, regulators, funders, and policymakers can act to strengthen ethical oversight of AI throughout the health research continuum. WHO also notes that most AI development remains concentrated in high-income settings and contends that strengthening leadership, capacity, and participation in AI in low- and middle-income countries will be important to ensuring the technology does not exacerbate existing inequities in health and health research.