Dengue antiviral mosnodenvir shows promise, but development stalls as disease spreads

A dengue antiviral pill, mosnodenvir, has shown the ability to prevent dengue infection in early human trials, marking a potential turning point in a disease long managed only with supportive care and public-health tools. The results come as dengue infections continue to rise and spread beyond traditional tropical regions, with warming temperatures pushing the disease toward southern Europe and the United States. Yet the drug’s sponsor, Johnson & Johnson, has stepped back from development, leaving a potentially transformative therapy without a current commercial partner and underscoring a broader retreat from infectious disease research by big pharma.

In a controlled laboratory-based study known as a challenge trial, 31 healthy volunteers in Baltimore and Vermont were deliberately exposed to dengue after taking mosnodenvir for several days. In the highest-dose group, 6 of 10 volunteers did not become infected at all, while the remaining participants in that cohort had lower viral loads and milder symptoms compared with those given a placebo. At lower doses, the drug delayed infection but did not prevent it entirely. Researchers described the results as a striking dose–response signal, with one Hopkins-trained infectious-disease scientist calling the data among the most compelling he had seen for a dengue antiviral.

Separately, field data from a 2023 trial across more than 30 sites in South America and Asia tested whether mosnodenvir could protect people living in the same households who are at high risk of exposure to the same mosquitoes. Among 265 participants who received the highest dose, not a single developed symptomatic dengue, while about 60 percent of those in the placebo group did. The field results have not yet undergone formal peer review, but the data have been posted publicly by the study teams. The findings, if replicated and extended, could support both prevention and early treatment uses for the drug, though timing remains a critical question because the disease progresses rapidly and the fever peak can occur before patients seek care.

The broader implications of mosnodenvir’s trajectory extend beyond the science. J&J announced last year that it would wind down its dengue antiviral program as part of a strategic shift toward non-communicable diseases like cancer and obesity. The decision leaves mosnodenvir without a sponsor to advance it into later-stage trials or potential regulatory approval. Ownership has since shifted back to KU Leuven, the Belgian university where the drug was first discovered before J&J licensed it for development. Patrick Chaltin, who runs the university’s drug discovery center, said the school intends to push forward with new partners and funding, including collaboration with the Wellcome Trust, to carry mosnodenvir into further testing.

The exit is part of a broader pattern: major pharmaceutical companies have pared back infectious-disease research while chasing blockbuster therapies for cancer, autoimmune disease, and obesity. Other dengue programs are still moving forward, underscoring a competitive but fragmented landscape. The Swiss drug maker Novartis is running a phase 2 trial of a separate antiviral, and the Serum Institute in India is testing a monoclonal antibody aimed at dengue. Drug development for dengue remains expensive and uncertain, and vaccines, bed nets, fogging campaigns, and public education about draining standing water continue to be the main tools for reducing transmission.

Mosnodenvir works by blocking replication of the dengue virus, suggesting it could help both prevent infection and treat people who are already infected. In theory, the drug could be useful if taken before exposure or shortly after, but the timing is crucial. Dengue virus tends to surge quickly, and patients often seek care after the most intense viral replication has already occurred. Treatment researchers hope mosnodenvir or a combination of similar antivirals could blunt progression to dengue hemorrhagic fever and organ failure, but the exact window for effective intervention remains a central question in ongoing work. Neelika Malavige, a dengue expert at the University of Sri Jayewardenepura in Sri Lanka, characterized the challenge as a potential breakthrough for a disease that has long lacked a proven antiviral.

The science also raises concerns about resistance. In the human challenge trial, genetic mutations emerged in the virus among nearly all participants who took mosnodenvir, mutations that could theoretically reduce the drug’s effectiveness over time. Moreover, certain dengue strains circulating in nature appear harder to treat with this class of antivirals. These realities reinforce the view that mosnodenvir, if it advances, would probably need to be part of a multi-drug strategy rather than a single solution. As Malavige noted, the dengue community’s goal is not to abandon prevention but to add a meaningful therapeutic option that can alter outcomes after infection.

For researchers, mosnodenvir offers a proof of concept that a dengue antiviral can work in humans—an achievement many decades in the making. Johan Neyts, a virologist at KU Leuven whose lab helped co-discover the drug, emphasized that if the amount of replicating virus can be reduced, the risk of progression to severe disease could fall. Still, the path forward is uncertain. Treatment trials were planned in Singapore to explore whether the drug could be used after infection, but the Covid-19 pandemic delayed those efforts, and by the time restrictions lifted, J&J had already stepped away from dengue, leaving a gap that may take years and new partnerships to fill.

The market reality adds another layer of complexity. The same forces that spurred J&J’s withdrawal—big pharma’s emphasis on high-margin, late-stage therapies—have led to a broader retreat from infectious disease research in recent years, with some industry observers labeling it a market failure. The hope now rests on KU Leuven and public funders to secure the resources needed to advance mosnodenvir and to attract additional developers willing to pursue dengue antivirals in combination with other agents. The Wellcome Trust and other philanthropic funders are seen as pivotal to bridging the translational gap, particularly for diseases that primarily affect lower-income countries.

The dengue threat itself is intensifying. The disease remains most common in South Asia and Latin America, but warming temperatures are pushing transmission into new regions, including parts of the United States and Europe. Texas, for instance, reported its highest dengue case count in two decades last year, including locally acquired infections, signaling that dengue is no longer exclusively a travel-related illness. Projections that by 2080 as much as 60 percent of the world’s population could live in areas where dengue can spread underscore the potential scale of the challenge. In places where dengue has long circulated, communities have learned to adapt to seasonal patterns, but the spread to new regions could strain health systems that already rely on vaccines and vector-control measures without a reliable antiviral readily available to patients.

If mosnodenvir can be developed and approved, it could become part of a multi-pronged approach to dengue that includes vector control, vaccines, and other antivirals. The first crucial step is securing sustained sponsorship and funding to move beyond early-phase studies into large, diverse clinical trials that can determine safety, efficacy, and practical use in real-world settings. The question now is whether the medical community, public health agencies, and funders can align to support the drug’s next phase, even as the market incentives for a dengue antiviral remain uncertain. In the meantime, the world’s largest mosquito-borne disease continues to exact a heavy toll, and public health tools to prevent infection, while essential, do not address the need for effective treatment after infection. The gap between what science has demonstrated and what the market will fund remains the central obstacle to turning mosnodenvir’s promise into a public-health tool that reaches patients who need it most.

As the research community awaits the next chapter for mosnodenvir, the dengue story continues to unfold against a backdrop of climate-driven expansion and a pharmaceutical industry rethinking where to invest. The ultimate test will be whether new partnerships can deliver a safe, effective antiviral at scale, and whether that antiviral can arrive in time to change the course of a disease that has long outpaced medicine. In the words of a leading dengue scientist, the dream remains simple: a patient who tests positive for dengue would receive an effective antiviral and move on with their life, free from the fear of a severe, life-threatening complication. The path to that reality, however, depends on funding, collaboration, and a willingness to pursue infectious diseases with the same urgency once reserved for other medical problems.

The dengue narrative is evolving—from a disease controlled primarily by public health tools to one where antivirals could shift the balance toward timely treatment. The next chapters will depend on whether mosnodenvir or another antiviral can be brought to market through new partnerships, with the global health community watching closely for a breakthrough that could save thousands of lives each year and alter the trajectory of a warming-world disease. The crucial question remains: who will finance the path from promising trial results to patient access? The answer will determine whether dengue finally has a weapon that changes its course for the first time in decades.