New Delhi: There may be nonetheless no particular drugs to deal with dengue, the Aedes mosquito-borne viral an infection that causes fever, headache, muscle and joint ache and, in some sufferers, can progress to bleeding, shock, organ failure and loss of life.
Now, a World Well being Group (WHO) evaluation of the worldwide dengue drug pipeline, published this month in The Lancet Microbe, has recognized six candidates with proof supporting additional improvement, though solely one of many six has reached Part 3 trials.
Researchers searched the WHO Worldwide Medical Trials Registry Platform (ICTRP), which brings collectively trial info from 20 registries throughout all six WHO areas.
The search retrieved 182 dengue clinical-trial data registered between 2005 and 2025. Of those, 74 had been final up to date in 2024 or 2025. Researchers then recognized 21 of those 74 data, involving 15 medicinal merchandise being investigated for dengue therapy, for an in depth evaluation, together with evaluation of obtainable efficacy proof.
Dengue is brought on by 4 virus serotypes and transmitted by Aedes mosquitoes. It’s endemic in additional than 100 international locations, with practically half the world’s inhabitants in tropical and subtropical areas in danger.
Most infections should not extreme, however some sufferers develop extreme dengue. A subsequent an infection with a unique serotype can carry a better danger of extreme illness.
The WHO reported a pointy international rise in dengue in 2023, with greater than 5 million circumstances and over 5,000 deaths throughout 80+ international locations and territories. About 80 p.c of reported circumstances have been within the Americas. The WHO attributed the unfold to components together with local weather change, increasing Aedes mosquito ranges, urbanisation and inhabitants motion, and assessed the worldwide danger as excessive.
In 2023, the WHO declared dengue its highest grade of emergency after a surge in circumstances and deaths. That 12 months, India reported 2,89,235 dengue circumstances and 485 deaths.
The emergency “highlighted the absence of protected and efficient dengue-specific therapies as a niche within the product panorama for take care of folks with dengue,” the WHO evaluation stated.
Up to now, dengue therapy stays supportive, with docs managing fluids, signs and problems and monitoring sufferers for indicators of extreme illness.
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The 6 candidates, and who’s creating them
The six candidates recognized by the WHO are taking totally different approaches to tackling dengue. Some purpose to cease the virus from multiplying, whereas others attempt to block the virus utilizing laboratory-made antibodies or management the physique’s inflammatory response.
Probably the most superior antiviral candidates is mosnodenvir (JNJ-1802), which works by focusing on a protein referred to as NS4B that the dengue virus must make copies of itself. The drug was developed by Johnson & Johnson (J&J) within the US, with analysis contributions from KU Leuven in Belgium.
However its improvement has since stalled. J&J discontinued its Part 2 discipline examine in 2024 as a part of a strategic reprioritisation of its infectious-disease programme. The corporate stated the choice was not associated to security issues.
One other method entails utilizing an current drug for a brand new goal. Fenretinide (ISLA-101), an older drugs, is being repurposed by Australia’s Island Prescription drugs as a possible dengue therapy and preventive remedy. Laboratory research have proven exercise in opposition to all 4 dengue virus sorts, and the corporate is now learning whether or not this may translate right into a helpful therapy in sufferers.
Like mosnodenvir, EYU688, being developed by Novartis in Switzerland, is designed to cease the virus from multiplying by focusing on the NS4B protein. In contrast to the 2 medication which have already accomplished Part 2 testing, EYU688 stays in Part 2, the place researchers are assessing whether or not it might probably scale back the quantity of virus within the blood, shorten fever and enhance different signs.
The opposite two candidates use antibodies slightly than standard antiviral medication. VIS513, initially developed by US-based biotech firm Visterra and later licensed to the Serum Institute of India (SII), is a laboratory-made antibody designed to recognise and fasten to the dengue virus and block its potential to contaminate cells.
It has now grow to be essentially the most superior out of the six medication. Its Part 3 trial in India is already enrolling adults and kids aged 5 years and above. Individually, SII partnered with the Medication for Uncared for Illnesses initiative (DNDi) in July this 12 months for worldwide testing. The bigger Part 3 trial, anticipated to enroll round 1,000 sufferers throughout Brazil, Malaysia and Thailand, is scheduled to start within the first quarter of 2027.
The fifth candidate AV-1, being developed by US-based AbViro, is designed to connect to a protein on the floor of the dengue virus and forestall it from inflicting additional an infection. It’s nonetheless in Part 2 trials.
The sixth candidate, Resomelagon (AP1189), takes a unique route altogether.
Developed by Sweden-based SynAct Pharma, it doesn’t straight assault the virus. As a substitute, it goals to manage the physique’s inflammatory response to an infection. That is necessary as a result of an extreme immune response can contribute to severe problems in dengue. The drug is getting into Part 2 testing in Brazil.
When the WHO performed its evaluation, three candidates — mosnodenvir, fenretinide and VIS513 — had accomplished industry-sponsored Part 2 trials in adults and had proven efficacy alerts equivalent to decreased quantities of virus within the blood or shorter period of signs.
EYU688 and AV-1 have been nonetheless being examined in Part 2, whereas Resomelagon was getting into Part 2.
What occurred to older medication, and what subsequent
The six candidates recognized by the WHO emerged after years of makes an attempt to repurpose current medicines for dengue. The evaluation checked out 13 Part 2 or Part 3 trials involving 9 such medication, however the proof was both inconclusive or didn’t assist additional improvement.
Montelukast, generally used for bronchial asthma and allergic reactions, confirmed promise in a small trial however failed to cut back extreme dengue in a bigger examine. Rupatadine, an anti-allergy drug, didn’t scale back development to extreme illness. Eltrombopag, used to deal with low platelet counts, elevated platelet numbers in dengue sufferers however didn’t scale back bleeding.
Different medication, together with celgosivir (an antiviral), chloroquine (an antimalarial), lovastatin (a cholesterol-lowering drug) and prednisolone (a steroid), additionally failed to point out convincing advantages.
Ribavirin, an antiviral used for different infections, fared no higher in early testing. It confirmed no protecting impact in opposition to dengue in an animal examine, and has no revealed human trial information to assist its use.
These outcomes spotlight a key problem in dengue drug improvement. Decreasing the quantity of virus within the blood doesn’t essentially translate into quicker restoration or a decrease danger of extreme illness.
WHO subsequently stated future trials have to measure outcomes that straight profit sufferers.
For non-severe dengue, WHO stated that there’s want for a protected therapy that works in opposition to all 4 dengue serotypes, shortens sickness and, ideally, prevents development to extreme illness.
It ought to ideally be an oral, short-course therapy that’s simple to manage, requires minimal specialised storage and is reasonably priced.
For extreme dengue, the WHO stated, the precedence is to forestall development to organ failure requiring intensive medical assist.
The WHO additionally recommends combining medication the place potential to cut back the danger of resistance, together with fast diagnostic checks to substantiate dengue an infection and allow therapy at an early stage.
(Edited by Ajeet Tiwari)
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