Tecovirimat Ineffective for Clade II Monkeypox
- Latest research presented at CROI 2025 sheds light on mpox treatment strategies.
- New data from an NIH-sponsored trial provides crucial insights for informing future mpox treatment decisions.The study focused on the antiviral drug tecovirimat, also known as TPOXX, and its...
- the international clinical trial, sponsored by the National Institutes of Health (NIH), revealed that tecovirimat monotherapy did not reduce the time to clinical resolution of clade II...
Tecovirimat Monotherapy Ineffective for Treating Clade II mpox in NIH-Sponsored Trial
Table of Contents
- Tecovirimat Monotherapy Ineffective for Treating Clade II mpox in NIH-Sponsored Trial
- Tecovirimat (TPOXX) and Mpox: Your Questions Answered
- What is mpox, and how is it spread?
- What are the different clades (types) of mpox?
- Is mpox a serious disease? Who is most at risk?
- What is tecovirimat (TPOXX), and how does it work?
- Was tecovirimat effective in treating mpox? What does the STOMP trial reveal?
- What does ”clinical resolution” mean in the context of the STOMP trial?
- What were the aims of the STOMP trial?
- What other factors were associated with faster mpox lesion resolution?
- Are there any approved treatments for mpox in the United States?
- Did the PALM007 study have similar results to the STOMP Trial?
- What does this mean for future mpox treatment strategies?
- Where can I find more facts on mpox?
- Tecovirimat for Mpox clinical Trial Comparison
Latest research presented at CROI 2025 sheds light on mpox treatment strategies.
Understanding the Study on Tecovirimat and Mpox
New data from an NIH-sponsored trial provides crucial insights for informing future mpox treatment decisions.The study focused on the antiviral drug tecovirimat, also known as TPOXX, and its effectiveness against the clade II mpox virus.
the international clinical trial, sponsored by the National Institutes of Health (NIH), revealed that tecovirimat monotherapy did not reduce the time to clinical resolution of clade II mpox lesions, nor did it improve pain control among adult participants.Consequently, trial enrollment was halted in late 2024 following an interim analysis that demonstrated the ineffectiveness of tecovirimat monotherapy within the study population. The detailed findings were unveiled at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.
Jeanne Marrazzo, M.D., M.P.H., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID), stated, “This study brought us a step forward in better understanding mpox disease and potential treatment strategies. We are grateful to the study team and participants for their contributions to groundbreaking research on a disease that we still do not know enough about.”
Mpox: Understanding the Virus and Its Clades
Mpox is caused by a virus primarily spread through close contact. Scientists have identified two main types, known as clades I and II. In 2022, a clade II virus subtype triggered a global mpox outbreak, and the virus continues to circulate at lower levels. A clade I outbreak in Central and East African countries in 2024 was declared a public health emergency of international concern. While travel-related cases of clade I mpox have been reported in the United States, the overall risk to the U.S.population remains low.
Individuals with compromised immune systems, certain pre-existing skin conditions, children, and pregnant women face a higher risk of developing severe mpox.
The STOMP Trial and Tecovirimat’s Role
The study of Tecovirimat for Mpox (STOMP) commenced in September 2022 as part of the U.S. government’s response to the clade II mpox outbreak. Currently, there are no mpox treatments approved in the United States.Tecovirimat, or TPOXX, received FDA approval for treating smallpox based on animal studies. Smallpox is caused by a closely related virus but typically results in a more severe disease than mpox. The STOMP trial, along with the PALM007 study in the Democratic Republic of the Congo, marked the first investigations of the drug in people with mpox. The PALM007 study reported findings in 2024 that mirrored those of the STOMP trial.
STOMP Trial Methodology and Results
STOMP was a randomized, international efficacy study conducted across multiple countries, including Argentina, Brazil, Japan, Mexico, Peru, Thailand, the United States, and Puerto Rico. Participants had experienced mpox symptoms for fewer than 14 days. The study employed a blinded approach, meaning neither the participants nor the investigators knew who received tecovirimat or a placebo.
Specific groups, including children, pregnant women, individuals with certain skin conditions or suppressed immune systems, and those with severe mpox, were assigned to an open-label study arm, where all participants received tecovirimat. The STOMP study aimed to assess the safety of tecovirimat and, in randomized arms, to evaluate whether a 14-day course of tecovirimat monotherapy reduced the time to clinical resolution of visible mpox lesions and improved other outcomes, such as pain, compared to a placebo.
Key findings from the randomized participants include:
- Participants reported experiencing mpox symptoms for a median of eight days before entering the study and had a median of nine mpox lesions.
- Approximately one-third reported severe pain.
- By day 29, an estimated 83% of participants receiving tecovirimat had reached clinical resolution, compared to 84% who received a placebo – a non-significant difference.
- Improvements in pain scores were similar between the tecovirimat and placebo groups.
- Viral DNA levels were not considerably diffrent between the two groups at either day eight or day 15.
- Adverse event rates were similar in both randomized study arms.
Exploratory analysis and Factors Influencing Mpox Resolution
An exploratory analysis of data from STOMP’s open-label arm sought to identify factors associated with faster mpox lesion resolution in participants with or at elevated risk of severe mpox. The analysis revealed that younger age and the absence of HIV (or viral suppression in those with HIV) were associated with faster clinical resolution. Though, no association was significant when considering the duration of symptoms before study entry. Researchers noted that STOMP open-label participants had fewer lesions but slower clinical resolution compared to the PALM007 trial.
Expert Commentary
Since the start of the clade II outbreak, clinicians treating mpox have had limited evidence to guide their practice, and STOMP provided definitive answers on the lack of clinical utility of tecovirimat monotherapy for the randomized population studied. Taken together, these latest results also highlight that we still have yet to isolate which factors influence mpox disease progression and clinical resolution.”
Timothy wilkin, M.D., M.P.H., chief of the Division of Infectious Diseases and Global Public Health at the University of California, San Diego
Study Details and Future Research
The STOMP study was conducted by the NIH-funded ACTG, a global clinical trials network focused on HIV and other infectious diseases. SIGA Technologies, Inc., provided tecovirimat for the study. The complete study results will be published in a scientific journal.
Tecovirimat (TPOXX) and Mpox: Your Questions Answered
This article addresses common questions about mpox and the effectiveness of tecovirimat (TPOXX) based on the latest research presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025.
What is mpox, and how is it spread?
Mpox, formerly known as monkeypox, is an infectious disease caused by the mpox virus. It’s primarily spread through:
Close contact: This includes direct contact with mpox lesions,body fluids,respiratory secretions,or contaminated materials like bedding.
Sexual contact: Mpox can spread during sexual activity.
Respiratory droplets: Prolonged face-to-face contact may also spread the virus.
What are the different clades (types) of mpox?
Scientists have identified two main clades of the mpox virus:
Clade I: Predominantly found in Central and East African countries. A 2024 outbreak of clade I was declared a Public Health Emergency of International Concern.
Clade II: This clade was responsible for the global mpox outbreak in 2022. While circulating at lower levels currently, it remains a health concern.
Is mpox a serious disease? Who is most at risk?
While most people recover from mpox, it can be severe, especially for:
People with compromised immune systems (e.g., those with HIV)
Children
Pregnant women
Individuals with pre-existing skin conditions
What is tecovirimat (TPOXX), and how does it work?
Tecovirimat, also known as TPOXX, is an antiviral drug. It was initially FDA-approved for the treatment of smallpox based on animal studies. Smallpox is caused by a virus closely related to mpox but typically results in a more severe disease.
Was tecovirimat effective in treating mpox? What does the STOMP trial reveal?
The NIH-sponsored STOMP (Study of Tecovirimat for Mpox) trial showed that tecovirimat monotherapy was NOT effective in reducing the time to clinical resolution of mpox lesions or improving pain control in the study participants infected with Clade II mpox. In the randomized, controlled trial, the outcomes for those receiving tecovirimat were statistically similar to those who received a placebo:
83% of participants receiving tecovirimat had reached clinical resolution by day 29.
84% of those receiving the placebo had reached clinical resolution by day 29.
Pain Improvements were also similar in the two groups
Viral DNA levels were not considerably diffrent between the two groups at either day eight or day 15.
Adverse event rates were similar in both randomized study arms.
Enrollment in the STOMP trial was halted early due to these findings.
What does ”clinical resolution” mean in the context of the STOMP trial?
Clinical resolution, in this case, refers to the complete healing of mpox lesions.
What were the aims of the STOMP trial?
The STOMP trial aimed to:
Assess the safety of tecovirimat.
Evaluate whether a 14-day course of tecovirimat monotherapy reduced the time to clinical resolution of mpox lesion and improved outcomes such as pain.
What other factors were associated with faster mpox lesion resolution?
An exploratory analysis of the STOMP data revealed:
Younger age was associated with faster lesion resolution.
The absence of HIV (or viral suppression in those with HIV) was associated with faster lesion resolution.
Duration of symptoms before study entry was not considerably associated with clinical resolution.
Are there any approved treatments for mpox in the United States?
Currently, there are no mpox treatments specifically approved in the United States.While tecovirimat is FDA-approved for smallpox, its use for mpox has been off-label.
Did the PALM007 study have similar results to the STOMP Trial?
Yes. The PALM007 study in the Democratic Republic of the Congo also indicated that tecovirimat was not effective as a monotherapy for mpox.
What does this mean for future mpox treatment strategies?
The STOMP trial highlights the need for further research to identify effective treatments for mpox. Future research may focus on:
Combination therapies
Targeting specific populations at high risk of severe disease
Identifying factors that influence mpox disease progression.
Where can I find more facts on mpox?
For more information on mpox, consult these reputable sources:
Centers for Disease Control and Prevention (CDC): cdc.gov
National Institutes of Health (NIH): nih.gov
* World Health Institution (WHO): who.int
Tecovirimat for Mpox clinical Trial Comparison
Here’s a comparison of the efficacy of tecovirimat between the STOMP trial and the PALM007 trial:
| Feature | STOMP Trial (Clade II) | PALM007 Trial |
| ———————— | —————————————————————- | ———————————————————————– |
| Intervention | Tecovirimat monotherapy vs. Placebo | Tecovirimat monotherapy ( No Placebo Group ) |
| Primary Outcome | Time to clinical resolution of mpox lesions | Clinical Resolution |
| Key Finding | No significant difference in time to resolution vs. placebo | Slower clinical resolution compared to STOMP open-label participants |
| Additional Findings | Younger age and absence of HIV associated with faster resolution | N/A |
| Overall Conclusion | tecovirimat monotherapy ineffective for Clade II mpox treatment | Not significantly effective, further research needed regarding combination |