A New Drug Candidate Could Change How We Treat Monkeypox—Here's Why It Matters

A biotech company has filed for orphan drug designation for NV-387, an experimental antiviral that could become the first effective treatment for monkeypox. This matters because the two drugs currently approved for monkeypox—tecovirimat and brincidofovir—have largely failed in real-world use, leaving patients with limited options as the virus continues to spread and mutate across Africa and beyond.

Why Current Monkeypox Treatments Aren't Working

When the World Health Organization (WHO) declared monkeypox a public health emergency in 2022, doctors hoped existing antivirals would help. But the results have been disappointing. Tecovirimat, marketed as TPOXX, showed no clinical benefit over standard care in a clinical trial for monkeypox patients and didn't reduce viral load. Even worse, some patients developed resistance to the drug.

Brincidofovir, sold as TEMBEXA, had a more troubling outcome. In a peer-reviewed study, three out of three monkeypox patients treated with brincidofovir developed drug-induced liver disease, forcing doctors to stop treatment. None of the patients showed any improvement. Despite these failures, a clinical trial of brincidofovir began in January 2025, though results haven't been publicly announced yet.

The core problem: monkeypox virus mutates rapidly, allowing it to escape both small chemical drugs and vaccine-induced immunity. Mutants resistant to the JYNNEOS vaccine have already been found, and the vaccine's antibody response is poor and short-lived.

How NV-387 Works Differently

NV-387 takes a fundamentally different approach. Rather than being a traditional small chemical drug that viruses can mutate around, NV-387 is a nanomedicine—a complete chemical nanomachine that mimics specific features on human cell surfaces that monkeypox needs to infect cells. Because the virus relies on these features to survive, it cannot escape them through mutation without losing its ability to infect humans.

The drug works independently of your immune system. It binds to virus particles, engulfs them, and destroys them directly—no antibodies or immune cells required. This is why resistance is unlikely, even as the virus continues to evolve.

In laboratory studies, NV-387 showed strong effectiveness against ectromelia, an orthopoxvirus closely related to both smallpox and monkeypox. It also completed a Phase I human trial in healthy adults with no reported adverse events, demonstrating safety and tolerability.

What Is Orphan Drug Designation and Why Does It Matter?

NanoViricides filed for orphan drug designation because monkeypox affects fewer than 200,000 people in the United States, qualifying it as a rare disease. Orphan drug status comes with significant benefits that can accelerate development and bring treatments to patients faster.

If approved, NV-387 would receive:

• Tax Credits: Qualified clinical trials would be eligible for tax credits, reducing development costs.
• Fee Exemptions: The company would be exempt from certain user fees charged by the FDA.
• Market Exclusivity: Seven years of exclusive market rights after approval, giving the company time to recoup development costs without generic competition.

The Broader Threat: Monkeypox Keeps Mutating

While monkeypox cases in the United States dropped to approximately 2,042 in 2025, the situation in Africa remains concerning. The more contagious monkeypox Clade Ia/Ib continues to spread and mutate across the African region, where the Africa CDC has declared it a "Public Health Emergency of Continental Security." WHO ended its international emergency declaration in September 2025, but the underlying threat persists.

"MPXV clade IIb is endemic in the USA. Further, the more contagious MPXV Clade Ia/Ib continues to simmer in Africa and is mutating, posing a potential global pandemic threat," said Anil R. Diwan, PhD, at NanoViricides.

Steps to Understanding NV-387's Development Path

• Current Stage: NV-387 has completed Phase I safety trials in healthy adults and is advancing toward Phase II clinical trials to test effectiveness in actual patients.
• Broad-Spectrum Potential: Beyond monkeypox, NV-387 has shown effectiveness in animal models against RSV, COVID-19, influenza, smallpox, and measles, suggesting it could address multiple viral threats.
• Timeline Uncertainty: The company cannot project an exact date for filing an Investigational New Drug (IND) application because development depends on external collaborators and consultants.

Why This Matters Beyond Monkeypox

The success of NV-387 could reshape how we approach viral infections more broadly. Traditional antivirals and vaccines work by targeting specific viral proteins, which viruses can mutate to escape. NanoViricides' approach—mimicking cell surface features the virus needs to survive—represents a new paradigm that could apply to multiple respiratory viruses and emerging threats.

For monkeypox specifically, an effective treatment would be transformative. Patients currently have few options beyond supportive care, and the virus's ability to mutate around existing drugs means we need new tools. NV-387 offers hope that we might finally have a weapon that the virus cannot easily escape.