The World Health Organization (WHO) has reaffirmed the global Public Health Emergency of International Concern (PHEIC) for mpox, amid rising case counts, evolving viral strains, and significant operational and funding challenges across affected regions. Against this backdrop, NanoViricides, Inc. has announced the near-finalization of its adaptive Phase II clinical trial protocol for NV-387, a novel oral antiviral designed to treat infections caused by monkeypox virus (MPXV) Clades Ia and Ib—predominantly circulating in Central Africa.
The Need for Better Therapeutics
Currently, no FDA-approved antiviral has demonstrated human efficacy against mpox. Tecovirimat (SIGA) failed to outperform standard of care in clinical trials. Brincidofovir was discontinued early due to liver toxicity in initial patients. While both were approved for smallpox under the FDA’s “Animal Rule,” neither has proven effective against mpox in clinical settings.
NanoViricides’ NV-387 seeks to help fill this critical gap. The antiviral is based on a unique host-mimetic nanomedicine platform that targets heparan sulfate proteoglycans (HSPG), a common receptor site used by over 90% of human pathogenic viruses. Unlike conventional antivirals that target viral components prone to mutation, NV-387 mimics host structures that viruses cannot easily evolve to avoid.
NV-387 was found to be safe in Phase I human trials, with no reported adverse events. Its oral gummy formulation—designed to dissolve in the mouth—also offers a practical advantage for mpox patients, many of whom suffer from painful oral lesions that hinder swallowing.
Trial Design: A Dual-Stage, Adaptive Protocol
NanoViricides’ upcoming clinical trial in the DRC will evaluate NV-387 in two phases. The Phase IIa portion involves a randomized, controlled comparison of 10 patients receiving NV-387 plus standard of care (SOC), and 10 receiving SOC alone. Dosing, tolerability, and efficacy will be assessed over multiple days of treatment and follow-up.
Results from Phase IIa will guide the Phase IIb stage, expanding to include up to 60 additional patients in a 2:1 treatment-to-control ratio. The trial may later extend to other affected countries depending on the outbreak trajectory and trial logistics.
Read also: New Strategic Framework for Mpox Outbreak Control and Medical Countermeasures
If successful, NV-387 would be the first antiviral to show human efficacy against mpox or any orthopoxvirus. Regulatory approvals are being pursued in parallel in the African region, with future filings planned for the U.S. FDA and European authorities.
A Complex and Expanding Epidemic
Mpox, once considered a rare zoonosis, has escalated into a multi-country epidemic affecting 17 nations in Africa, with sporadic Clade I cases detected in high-income countries including the United States. WHO’s Emergency Committee cited sustained transmission, limited vaccination coverage, and weak health systems as justification for the July 2025 PHEIC extension.
Despite the deployment of 2.9 million vaccine doses across affected regions, only about 724,000 have been administered, hindered by security concerns, supply chain constraints, and underfunded local public health infrastructures. In the Democratic Republic of the Congo (DRC), two million doses have been delivered but less than a third have reached the population. The co-circulation of Clade Ia and Ib viruses in these regions—each with higher case fatality rates than Clade IIb strains seen in the West—underscores the urgency of effective therapeutics.
Implications for Global and National Health Security
The continued spread of Clade I mpox poses not only a humanitarian crisis in Africa but also a latent risk to global health. Travel-related importations of Clade I strains—though not yet causing sustained transmission—illustrate how localized failures in containment can trigger broader public health emergencies. Given mpox’s zoonotic origin and evolving transmission dynamics, including increasing cases among children and immunocompromised populations, preparedness cannot be confined by borders.
Read also: Tecovirimat Shown to Lack Efficacy as Treatment for Clade II Mpox
For the general public, investment in antiviral development is not an abstract exercise. It is a cornerstone of pandemic readiness. A safe, effective, and easily deployable therapeutic like NV-387 could limit viral spread, reduce disease severity, and serve as a strategic countermeasure against bioterrorism threats such as smallpox. In this regard, the U.S. and other nations have a vested interest in ensuring robust support for drug development and international disease control efforts.
The Road Ahead
Mpox’s continued designation as a PHEIC reflects the challenges of combating an evolving virus with limited tools. As vaccine coverage lags and health systems remain under strain, NV-387 represents a promising avenue for therapeutic intervention.
While global funding gaps remain—WHO’s $145 million request for mpox response remains unmet—collaborative investments in diagnostics, vaccines, and therapeutics will be vital. The progress of NV-387’s clinical trial may serve as a model for future antiviral development and a beacon of hope in an otherwise constrained outbreak response landscape.
Sources and Further Reading:
- NanoViricides, Inc. – Official Site and Press Releases
- CIDRAP: Mpox drug Tpoxx didn’t speed lesion healing in Clade 1 patients, trial shows
- CIDRAP: Trial stops enrollment after Tpoxx fails to speed Clade 2 mpox healing or pain relief
- Global Biodefense: WHO Emergency Committee on Mpox – July 2025 Update
- MPX-Response: MOSA Clinical Trial Overview
- SIGA Technologies 2024 Annual Report to SEC
Editor’s note: The disease caused by monkeypox virus is now officially called mpox, following a 2022 renaming by the World Health Organization to reduce stigma and improve public communication. While mpox refers to the illness, monkeypox virus (MPXV) remains the accepted scientific name for the virus itself.