Monoclonal for Dengue Shows Promise in Hospitalized Cases

An investigational monoclonal antibody targeting dengue virus (Dengue-mAb) safely reduced viral loads and infection symptoms, according to a placebo-controlled phase II trial in India.

Among 249 adults hospitalized with dengue and a history of fever, those randomized to one of four doses of Dengue-mAb achieved significantly greater viral log reductions 24 hours after treatment compared with placebo. The differences in adjusted least squares means were:

• 0.77 lower for 3 mg/kg (P=0.02)
• 1.12 lower for 5 mg/kg (P=0.003)
• 1.16 lower for 7 mg/kg (P<0.001)
• 1.21 lower for 9 mg/kg (P=0.001)

Dengue-mAb, given as a single-dose intravenous infusion, also outperformed placebo when it came to reducing the presence of virus in the blood. Eight hours after treatment, 50% of placebo patients were negative for viremia compared with 71.4% for the 3 mg/kg group and 100% for the three higher-dose groups.

No one in any of the study’s five groups had a treatment-related serious adverse event, reported researchers led by Prasad Kulkarni, MD, of Serum Institute of India in Pune, in JAMA Network Open.

“This is, to our knowledge, the first evidence of a preliminary therapeutic effect in patients with dengue,” Kulkarni and colleagues wrote. “Although the number of patients is small, the observed significant reductions in viremia, RNAemia, and fever clearance may lead to reduction in severity of illness and decline in transmission of dengue.”

Transmitted through mosquito bites, dengue virus infection is the fastest-growing mosquito-borne disease globally. There were a record 14.1 million dengue cases and 9,508 deaths reported worldwide in 2024, with a 0.07% case fatality rate. Dengue is more common in tropical and subtropical regions, but reported U.S. dengue cases surged in 2024, climbing to 3,798 cases that year, up sharply from an annual average of 828 cases during 2010-2023, according to the CDC.

Most infections are asymptomatic or mild, with common symptoms including headache, fever, body aches, nausea, and rash, but severe dengue can cause neurologic complications, such as Guillain-Barré syndrome, and death.

There are three licensed vaccines to prevent dengue but no approved antiviral to treat it. Standard therapeutic approaches include pain management and hydration.

The study enrolled 250 adult patients at 12 tertiary-care hospitals in India from September 2021 to May 2023 (one randomized participant withdrew consent before dosing and was excluded from the full analysis). Patients were ages 18 to 60 years, presented to a hospital within 48 hours after onset of fever, and had dengue confirmed through a rapid antigen test.

The study’s primary outcomes were viral log reductions at 24 hours after treatment, and the percentage of patients with causally related serious adverse events.

Among the patients with fever at baseline, 92.9% of the 3 mg/kg group, 100% of both the 5 mg/kg and 7 mg/kg groups, and 94.1% of the 9 mg/kg group had fever clearance 24 hours after treatment, compared with 58.3% of the placebo recipients.

In patients who had dengue virus RNA in the blood at baseline (roughly half of each group), 7.4% of placebo patients were negative 24 hours later, compared with 29.2% of patients randomized to Dengue-mAb 3 mg/kg, 28% of the 5 mg/kg group, 25% of the 7 mg/kg group, and 22.7% of the 9 mg/kg group.

Overall, 23.3% of patients had an adverse event, including 20% of those in the placebo group and 20% to 32% of those in the four Dengue-mAb groups. All 13 treatment-related adverse events were in Dengue-mAb patients, but all recovered with no sequelae.

Study limitations, according to Kulkarni and co-authors, included lower than predicted baseline viremia and RNAemia, which may indicate that participants were treated more than 48 hours after fever onset.

Phase III trials of Dengue-mAb are underway in India and slated to start next year in Brazil, Malaysia, and Thailand.