There’s a reason dengue infections are also called “breakbone fever.”

Along with a mild fever, symptoms of the mosquito-borne illness include bone-deep, aching pain in the joints and behind the eyes. In severe cases, blood vessels begin to leak. And in the worst cases, that can lead to organ failure.

More than 14 million people contracted dengue last year, and the real number is likely several times higher. While it remains most common in South Asia and Latin America, it’s no longer just a tropical disease. Warming temperatures are pushing dengue into southern Europe and the United States. Last year, Texas saw its highest case count in two decades, including locally acquired infections, meaning the virus is now circulating here, not just arriving with travelers.

The public health tools we have — the dengue vaccines, bed nets, fogging campaigns, public awareness to drain standing water — are all aimed at keeping mosquitos at bay and preventing infections in the first place. There’s nothing for after: no antivirals — nothing like Paxlovid for Covid, or Tamiflu for the flu, or artemisinin for malaria. Once you’re sick, the strategy is just supportive care and hope.

Earlier this month, though, that changed.

A new antiviral pill for dengue called mosnodenvir showed promising results in early phase 2 trials. In a study where volunteers were deliberately exposed to dengue, roughly half of those who received the highest dose never got sick at all. For a field that has struggled for decades to find an effective antiviral, it’s the clearest evidence yet that a drug can prevent dengue — and researchers believe the same pill could eventually treat people who are already infected.

But, even before the results were published, Johnson & Johnson, the American pharmaceutical giant that developed mosnodenvir, had already abandoned any efforts to bring the drug to market.

Last year J&J announced it would wind down its dengue antiviral work, with a “strategic reprioritization” of its research toward non-communicable diseases like cancer and obesity. What this means is that one of the most promising dengue drugs ever tested is now without a pharma sponsor, waiting for someone else to carry it forward.

André Siqueira, who heads the dengue program at the Drugs for Neglected Diseases Initiative (DNDi), said mosnodenvir is “very, very promising” and said he wants to see it pushed into further trials “as quickly as possible.”

But why — if the drug shows much promise — would its maker walk away?

J&J’s exit isn’t an outlier; it’s part of a broader retreat from infectious disease research across the pharmaceutical industry, as companies shift toward drugs for wealthier markets: cancer, obesity, autoimmune disorders.

Dengue already kills thousands every year, and it’s getting worse. By 2080, climate models suggest, nearly 60 percent of the world’s population could be living in areas where dengue spreads.

And, in this new world, watching the first antiviral pill that works against dengue get abandoned — while the disease spreads to new continents — reveals the gap between the drugs we need and the drugs the market will deliver.

What the pill actually proved

To test whether mosnodenvir actually works, researchers did something uncommon: They deliberately infected people with dengue.

Over the past three years, 31 volunteers in Baltimore and Vermont, in what’s called a challenge trial, agreed to take a pill for several days and then get injected with a weakened dengue virus. It’s a faster way to get answers than waiting for people to get sick naturally, but it requires volunteers willing to sign up for a controlled case of dengue.

Among people who got the highest dose of mosnodenvir, 6 out of 10 never developed an infection at all. The other four had much lower levels of virus in their blood and milder symptoms than the placebo group, where everyone got sick. At lower doses, the drug delayed infection but didn’t prevent it — a clear signal that the higher dose was doing something real.

“It’s one of the most beautiful dose-response results I’ve seen,” Anna Durbin, the Johns Hopkins researcher who led the study, told Science last month.

Then, there’s the field data. In 2023, J&J launched a trial across more than 30 sites in South America and Asia to test whether the drug could protect people in the same household who are at high risk of getting bitten by the same mosquitoes. Among 265 people who received the highest dose, not a single person developed symptomatic dengue. In the placebo group, 60 percent did. (This data hasn’t been formally peer-reviewed yet, but it’s posted publicly.)

For Neelika Malavige, a prominent dengue researcher at the University of Sri Jayewardenepura in Sri Lanka, the significance goes beyond the numbers. “It’s a huge scientific breakthrough just doing the study,” she said, referring to the design of the challenge trial itself, which had never been done for a dengue antiviral before. For a disease with no approved treatment, this is as close to proof of concept as it gets.

“The dengue community may be closer than ever to a long-awaited treatment,” Xuping Xie of the University of Texas Medical Branch wrote in a commentary accompanying the paper.

But, there are some caveats

The trial proved that mosnodenvir can prevent infection, a first for any dengue drug. But prevention isn’t what dengue doctors need most. What they need is a treatment, something to give patients who are already sick to keep them from getting worse.

That’s what makes an antiviral so valuable. Prevention strategies have a ceiling; you can reduce mosquito populations, but you can’t eliminate them, and warming temperatures keep pushing them into new territory. A drug that works after exposure would be the first tool that doesn’t depend on stopping the mosquito first.

The hope is that the same drug could do both. Mosnodenvir works by blocking the virus from replicating, and, in theory, that should help whether you take it before you’re infected or shortly after. The question is timing.

That’s where dengue gets tricky. Unlike malaria, where the parasite lingers, and you can kill it with drugs, the dengue virus moves through the body notoriously fast. By the time a patient feels sick enough to see a doctor — usually a few days into the fever — the virus is often already on its way out. The brutal symptoms that follow, the blood vessel leakage and organ damage, are driven largely by the body’s own immune response, not the virus itself.

This is why antivirals have been so hard to develop for dengue. The window to intervene can be narrow, and for many patients, it’s already closing by the time they show up.

The scientists who developed mosnodenvir believe it could work as a treatment. “If you reduce the amount of replicating virus, you will also reduce the likelihood that the patient evolves towards severe disease,” said Johan Neyts, a virologist at KU Leuven whose lab co-discovered the drug. The logic is in line with how antivirals for, say Covid, work, but this hypothesis hasn’t been tested in humans. Treatment trials were planned in Singapore, but the Covid pandemic made them impossible. By the time restrictions lifted, J&J had already decided to exit.

The dream, Malavige said, is simple, “You go to the doctor, get yourself tested, the test is positive, you’re given an antiviral, and that’s the end of the story.” The question is whether patients can get there early enough — and whether mosnodenvir can work.

There’s also the question of resistance. In the human challenge trial, genetic mutations emerged in the virus among nearly all the participants who took mosnodenvir — mutations that could, in theory, make the drug less effective over time. And some dengue strains already circulating in nature appear to be harder to treat with this type of drug.

This is a real limitation. Mosnodenvir alone probably isn’t a long-term solution, because, eventually, the virus might adapt. But that problem is a familiar one for drug makers. HIV and malaria both evolved resistance to early drugs, and the answer was combination therapy: multiple drugs that attack the virus in different ways, making it far harder to escape all of them at once.

For that strategy to work with dengue, though, we need more drugs to combine. Mosnodenvir may not be the whole puzzle, but it could be the first piece. “If people stopped at the first sign of seeing trouble,” Malavige said, “then the world will not progress.”

Could Mosnodenvir…get adopted?

Johnson & Johnson’s exit follows a well-worn path for big pharma.

Over the past two decades, Bristol Myers Squibb, Novartis, AstraZeneca, and other major drugmakers have all scaled back or abandoned infectious disease research, judging that these drugs simply couldn’t compete with cancer and obesity blockbusters. A recent op-ed in the Financial Times called it a “textbook market failure.” The public health impact is massive, but the financial returns for addressing them aren’t.

After J&J’s exit, ownership of mosnodenvir is being transferred back to KU Leuven, the Belgian university where the drug was first discovered before J&J licensed it for development. “We will do all we can to make sure that mosnodenvir is further developed in clinical trials as soon as possible,” said Patrick Chaltin, who directs the university’s drug discovery center. To do that, the university is working with the Wellcome Trust, a major global health funder, to find new partners and funding.

And fortunately, mosnodenvir isn’t the only dengue drug that the pharmaceutical industry is looking into. The Swiss drug maker Novartis is running a phase 2 treatment trial for a different antiviral, and the Serum Institute in India is testing a monoclonal antibody.

Drug development is expensive and uncertain, and the people who need dengue treatments most are not the people who can pay the most. But these steps are encouraging.

In countries where dengue has always circulated — India, Brazil, the Philippines, Sri Lanka — people have learned to live around it, says Malavige. Life bends around when the mosquitoes are biting, and then bends back.

But dengue isn’t locked in those places anymore. Warmer temperatures are carrying the mosquitoes — and the virus — somewhere new every year. And there’s no sign that this expansion is slowing down.