Breakthroughs Blog: Medicines

We have made significant global progress against malaria over the last few decades, with three countries officially eliminating the disease just last year, joining the ranks of nearly 50 countries worldwide that have now achieved malaria-free status. Yet, malaria remains a formidable global challenge, with an estimated 282 million cases and 610,000 deaths in 2024, roughly 9 million more cases than in 2023. Climate change, conflict and instability, and funding disruptions all contribute to this persistent threat.  The rise of drug and insecticide resistance, a decades-old obstacle, has drawn renewed attention as it threatens to erode years of momentum. New tools addressing resistance, including novel drug combinations and vector control tools, offer hope for regaining lost ground. The long history of antimalarial drug resistance and new innovations to curb its riseAntimalarial drug resistance dates back nearly 75 years. Resistance to chloroquine, once of the most widely used antimalarial drugs, was first detected in the 1950s and spread unchecked for decades, contributing to a global rise in malaria-related mortality. Varying degrees of resistance also emerged to the therapies introduced to replace chloroquine. By the time artemisinin-based therapies were widely introduced in the 1990s, the World Health Organization took proactive steps to protect their efficacy by recommending they be used only in combination with other drugs.Artemisinin-based combination therapies (ACTs) have since become the global standard treatment. However, partial resistance to artemisinin-based drugs has now been confirmed or suspected in at least eight African countries, and several of the drugs used in combination with artemisinin are also showing declining efficacy. Emerging therapies in late-stage development could help address these growing challenges.In fall 2025, Novartis announced positive Phase 3 results for a novel, non-artemisinin combination malaria therapy developed with the Medicines for Malaria Venture. Delivered as a once-daily packet of oral granules taken over three days, the therapy was found to be highly effective against multiple forms of the malaria parasite and was also able to kill drug-resistant strains. If approved, it would represent the first major innovation in malaria treatment since ACTs.Another promising approach in late-stage development is triple ACTs, which combine artemisinin-based drugs with two additional drugs to fend off the emergence of resistance. In fall 2025, the Mahidol Oxford Tropical Medicine Research Unit, with funding from the Global Health Innovative Technology Fund, launched the first Phase 3 trial of a fixed-dose triple ACT in Rwanda. Taken once daily for three days, the therapy is designed to be affordable, easy-to-administer, and suitable across age groups, supporting adherence and reducing the risk of incomplete treatment, a key driver of resistance.  Historical lessons and new frontiers in vector control tools to tackle insecticide resistance Beyond parasite resistance, widespread insecticide resistance in mosquito vectors—dating back to the 1950s—has reduced the impact of existing vector control tools. The widespread uptake of insecticide-treated bednets helped drastically reduce malaria cases in Africa over recent decades, but most nets deployed since 2000 relied on pyrethroid insecticides. Resistance to pyrethroids is now widespread.In response, the World Health Organization recommended the first next-generation insecticide-treated nets in 2017. Since then, global partners, including the Innovative Vector Control Consortium, PATH, and the Gates Foundation, have collaborated to deploy more than 56 million of these new-generation nets, which have been shown to significantly improve malaria control outcomes.Additional innovations in the pipeline could complement these next-generation bednets. One promising group of tools is endectocides, or medicines taken by humans that kill mosquitoes when they bite. Ivermectin, an antiparasitic drug long used in mass drug administration campaigns for neglected tropical diseases, is the most studied endectocide to date. A 2025 study led by the Kenya Medical Research Institute, the Barcelona Institute for Global Health, and the Manhiça Health Research Center found that mass administration of ivermectin reduced new malaria infections by 26 percent when implemented alongside standard vector control measures. Unlike bednets or indoor residual spraying, which are limited to certain places or times of day, endectocides can protect people from malaria wherever they are.Early-stage research is also exploring gene drive technology, which genetically modifies mosquito populations to reduce their ability to transmit malaria. Target Malaria is investigating several gene drive approaches, including one of its most promising strategies: modifying male mosquitoes to carry a gene that causes some females to become sterile. Another approach involves genetically modifying males to produce predominantly male offspring, which can decrease mosquito numbers over time and reduce parasite transmission, since only female mosquitoes bite and transmit malaria. While still early in development, these tools could one day offer a transformative way to control mosquito populations.Drug and insecticide resistance represent some of the most urgent threats to the global fight against malaria, but they are not insurmountable. History shows that sustained innovation can blunt the impact of emerging resistance and help restore progress. Increased investment in new tools, alongside global coordination to ensure rapid and equitable deployment, will be essential to accelerating progress against malaria in the years ahead.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted a positive opinion to a new and simpler treatment for sleeping sickness, a serious vector-borne disease found in rural sub-Saharan Africa, for which the current treatment can be long and challenging. The Drugs for Neglected Diseases initiative (DNDi) and Sanofi co-developed a single-dose oral treatment, acoziborole, for both early- and advanced-stage infections in people 12 and older, which was found to be highly effective in a pivotal clinical trial. The endorsement will support further regulatory approval and rollout. Sanofi has pledged to donate doses to the World Health Organization, helping improve access to the new drug in the places where it’s most needed. Another study underway is testing the drug in children between 1 and 14 years old. The Global Antibiotic Research and Development Partnership (GARDP) recently announced that it has acquired all data and licensing rights for apramycin, an antibiotic introduced in the early 1980s to treat serious bacterial infections in animals, to evaluate its potential as a promising antibiotic against drug-resistant infections in humans. The drug has shown potential for human use in preclinical trials, but early-stage development stalled after the company developing it closed. The organization has planned a Phase 1 study set for 2027 to assess safety and pharmacokinetics. Last week, the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) announced that it’s awarding $1.2 million to Harvard University’s Andrew G. Myers Research Group to develop novel antibiotics for multidrug-resistant bacteria like Escherichia coli and Klebsiella pneumoniae, which cause serious infections around the world. Despite their significant global threat, the pipeline for novel antibiotics against these priority pathogens is lacking. The Harvard team will use the funding to further preclinical development of a new class of antibiotics that target a critical part of multidrug-resistant bacterial pathogens that plays a key role in the pathogens’ ability to cause infection and evolve drug resistance, which the researchers hope will be able to overcome drug-resistant infections without contributing to the emergence of broader cross-resistance.  

A Phase 2 trial in The Gambia found that a vaccine for enterotoxigenic Escherichia coli (ETEC), a leading cause of diarrheal disease in children in low-income countries, was safe and effective in children between 6 and 18 months old. Cases of ETEC are expected to increase in the coming years due to climate change, and the vaccine under study, ETVAX, the most advanced of the several ETEC vaccines in the pipeline, could help reduce illness and death, lower health care costs, and curb the growing threat of antimicrobial resistance. The vaccine will now advance to a large multicountry Phase 3 trial for further evaluation. A research team at the University of Buffalo has developed an inhalable drug-delivery system for treating tuberculosis (TB), which could reduce the frequency of dosing and lessen side effects. Standard treatment for TB can be lengthy and require multiple drugs, with unpleasant side effects, leading some patients to stop treatment— contributing to the emergence of drug-resistant TB. The new approach involves an inhalable nanoparticle system that modulates the immune system and carries rifampin, a common TB drug, directly to the lungs, where TB bacteria primarily reside. This targeted method contrasts with the pill formulation of rifampin, which, when taken orally, only delivers limited amounts of the drugs to lung tissue. Further studies will explore whether the nanoparticle system can deliver combination treatments, which are the cornerstone of TB treatment, and whether the system can be adapted to address other lung diseases. Ghana recently became the first-ever country to approve a new single-dose combination treatment for soil-transmitted helminths, which cause parasitic infections that affect millions in endemic regions in Africa. The regimen is as safe as the standard drug used in mass deworming campaigns and demonstrates improved efficacy against whipworms, which are often resistant to the single-drug treatment. The medicine is also fruit-flavored, fast-dissolving, and incorporates a novel age-based dosing strategy, making it suitable for children. Administering the two drugs incorporated in the combination treatment previously required between two and six pills per person. 

A two-year citywide experiment in Singapore found that releasing Wolbachia-infected mosquitoes was effective at reducing mosquito numbers and dengue transmission in the densely populated city, supporting their use as a complement to existing vector control methods and vaccines to control transmission of dengue and other mosquito-borne diseases. Wolbachia is a common type of bacteria found in insects that cannot make people or animals sick but can stop the dengue virus from replicating inside the Aedes aegypti mosquitoes that spread dengue and other viruses, reducing mosquito populations and disease transmission. The researchers divided the city into clusters, releasing sterile infected male mosquitoes in some areas while leaving other areas untouched. They found that where the infected mosquitoes were released, mosquito numbers fell sharply, and people living there were about 70 percent less likely to develop symptomatic dengue after a few months of exposure. A Phase 4 randomized controlled trial has provided further evidence of the safety and efficacy of shortened regimens of preventive tuberculosis (TB), which could help improve uptake and completion rates. The trial, conducted in Brazil, tested one- and three-month regimens of isoniazid and rifapentine, much shorter than the current standard regimen of isoniazid, which lasts six to nine months and has seen poor uptake and completion rates. Additional studies are needed to ensure safety and acceptability across diverse populations. A Stanford University research team has developed an affordable, battery/solar-operated microscope called Octopi that uses artificial intelligence (AI) to automatically diagnose malaria in blood samples in minutes, which could greatly improve access to early and accurate diagnosis in low-resource settings. Confirmatory malaria diagnosis is currently done through a long, technical process carried out manually by lab technicians. The team also developed a complementary tool to automate and standardize the process of preparing blood samples, which is open source, requires no electricity, and is cheap.