Antiviral for dengue shows promise, but drug maker exits, leaving future uncertain

A dengue antiviral shown to prevent infection in early trials marks a rare breakthrough for a disease with no approved treatment, but development remains in limbo as the sponsor exits. Mosnodenvir, developed by Johnson & Johnson, prevented infection in a controlled study where volunteers were deliberately exposed to dengue.

Dengue, the world's biggest mosquito-borne disease by infection numbers, affected more than 14 million people last year, with likely many more uncounted cases. The burden is rising in parts of the world as warming temperatures push the virus into southern Europe and the United States, including Texas, which reported its highest case count in more than two decades, including locally acquired infections.

The drug works by blocking the virus’s ability to replicate, potentially offering protection before infection and a possible treatment if given soon after exposure. Dengue is challenging because most severe damage results from the body's immune response, not only the virus itself, and the timing of intervention is critical.

In a deliberate infection study conducted in Baltimore and Vermont in the past three years, 31 volunteers took mosnodenvir or a placebo before being exposed to dengue. Among those who received the highest dose, six of ten did not develop an infection, while the others had lower viral levels and milder symptoms than in the placebo group. At lower doses, infection was delayed rather than prevented.

A separate field trial conducted in 2023 across more than 30 sites in South America and Asia tested whether the drug could protect people in the same household from dengue. Among 265 participants given the highest dose, none developed symptomatic dengue, while about 60 percent of those in the placebo group did. The data have not yet undergone formal peer review, but were posted publicly.

Researchers and public-health advocates described the results as a potential proof of concept for a dengue antiviral. The study design, including the challenge trial, was hailed as a milestone for a disease with few antiviral options. If the drug can be developed further, it could eventually treat people who are already infected, in addition to preventing infection.

But the findings also underscore a major gap: while a preventive effect is encouraging, dengue doctors need treatments for patients who are already sick to prevent progression to severe disease. Because dengue virus levels peak early, the window for effective antiviral use is narrow, and timing will influence how useful mosnodenvir could be in real-world care.

Even if mosnodenvir can be used after exposure, resistance is a concern. In the human challenge trial, viral mutations emerged in participants who took mosnodenvir, suggesting the virus could adapt. Some circulating dengue strains already appear more difficult to treat with this class of drug. As a result, any long-term solution would likely require combinations of drugs that attack the virus in different ways.

Johnson & Johnson announced last year that it would wind down its dengue antiviral program to focus on other disease areas, a move that leaves mosnodenvir without a sponsor. The drug’s ownership has been returned to KU Leuven, the Belgian university where the compound was discovered, and the university is seeking partners and funding, including support from the Wellcome Trust, to advance further trials.

Other drug developers are pursuing dengue antivirals or related strategies. Novartis is running a phase 2 program for another antiviral, and the Serum Institute of India is testing a monoclonal antibody. The broader trend in the pharmaceutical industry has been a retreat from infectious diseases as firms chase assets in cancer, obesity, and autoimmune disorders, a pattern some analysts describe as a market failure in this area.

Public-health officials note that dengue already kills thousands each year and that warming temperatures could expand the virus’s reach. Climate models project that by 2080 as much as 60 percent of the world’s population could live in areas where dengue transmission is possible, highlighting why a viable antiviral would be a critical tool alongside vaccines, bed nets, and vector-control campaigns. The struggle to fund and bring such drugs to market underscores the gap between what is needed and what the market will bear.

In the near term, researchers and funders say the next steps are to attract new sponsors for mosnodenvir and to test it as a treatment in people who are already infected. Beyond this drug, the dengue research community anticipates a pipeline of candidates and a broader strategy that combines antivirals with vaccines and vector-control tools to reduce transmission and disease severity.