Interim Analysis of STOMP Study Shows No Efficacy of Tecovirimat in Mild to Moderate Mpox Cases

An interim data analysis from an international clinical trial called Study of Tecovirimat for Mpox (STOMP) concluded that antiviral medication tecovirimat did not decrease lesion resolution time or have any bearing on pain among adults with mild-to-moderate Clade II Mpox who are at low risk of severe disease progression and show no negative safety concerns with regard to treatment with it.

At this point, the Data Safety and Monitoring Board of the study recommended stopping further enrollment of participants randomized between tecovirimat or placebo; given this finding, study sponsor National Institutes of Allergy and Infectious Diseases (NIAID), accepted this advice; because there wasn’t an efficacy signal yet for either treatment group, an open-label arm designed specifically to evaluate efficacy was closed down as well.

STOMP findings provide essential knowledge that informs clade II mpox medical countermeasures, while emphasizing the significance of conducting well-designed, randomized clinical trials during infectious disease outbreaks. Since no treatments had ever been tested before 2022, this trial serves to systematically test existing antivirals such as tecovirimat while simultaneously seeking new antivirals or antibody-based therapeutics as possible solutions to treat people living with MPox virus infection.
Jeanne Marrazzo, M.D., MPH is currently Director of NIAID.

Mpox is caused by a virus that spreads primarily through close personal contact. Two strains, known as Clades I and II have been identified; historically present in Central Africa as well as Western Africa respectively. 2022 witnessed a global mpox outbreak caused by clade II subtype virus; low levels are still prevalent today. By 2024, however, an outbreak in Central and East African nations was declared as an international public health emergency by World Health Organization. Travel-related cases of Clade I Mpox (clade I Mpox) have been confirmed worldwide and in the US on November 15; with only low risk estimates to the public. People with compromised immune systems or certain preexisting skin conditions, children, and individuals pregnant are at greater risk for severe M. Pox infections. TPOXX was initially approved by the Food and Drug Administration to treat smallpox; an infection which is closely related but much more dangerous than that which causes mpox; but its safety and efficacy as an antiviral treatment were unproven before this year.

STOMP study began in September 2022 as part of an integrated U.S. response to the Clade II Mpox outbreak. This international efficacy study recruited participants who had been sick with mpox for less than 14 days across Argentina, Brazil, Japan, Mexico, Peru, Thailand and the US (including Puerto Rico). Participants were then randomly allocated either tecovirimat or placebo treatment according to two-to-one ratio. Blinding of participants and investigators was used during this trial; neither knew which group received either tecovirimat or placebo. Children, pregnant people and other participants with severe diseases, certain skin conditions or immunological suppression were included in an open-label study arm; that means all participants received the drug instead of being randomly chosen to participate. The STOMP Study provided safety assessments to all participants as well as an independent, blinded evaluation to see whether a 14-day course of tecovirimat reduced clinical resolution time for visible MPOX lesions while simultaneously improving other measures like pain. It found tecovirimat to be significantly better at doing both than placebo in this respect.

At 75% of its target enrollment, an interim analysis conducted prior to treatment with tecovirimat showed no difference in time to lesion resolution between participants treated with this agent and those receiving placebo treatment. Pain decreased similarly among participants who received both tecovirimat and placebo treatments. At the request of the DSMB, a further assessment was conducted that demonstrated there was less than 1% chance that enrollees and follow-up would demonstrate effectiveness with tecovirimat were it to complete enrollment and follow up, given its design and available data. At the time of analysis, reported adverse events were low and comparable between tecovirimat and placebo. Due to design, STOMP cannot draw definitive conclusions regarding its efficacy in participants at high risk for severe Clade II MPox infections or with current severe cases.

Further analyses of study data are ongoing and study participants are being informed about findings; clinicians will develop personalized clinical care plans based on disease severity and symptoms for every participant in accordance with clinical trial findings. In addition, the Centers for Disease Control and Prevention (CDC) offers an expanded access investigational new drug (EA-IND) protocol for treating MPox outside research settings; eligible persons include people suffering severe immunocompromise including advanced HIV for whom its role has not yet been fully determined through clinical trial participation. For further details regarding this EA-IND protocol please see their Web page at CDC Website

“STOMP stands out for its rapid launch, inclusive nature, and partnership among governments and public health authorities” according to study chair Timothy Wilkin M.D. MPH chief of Infectious Diseases & Global Public Health at University of California San Diego Timothy Wilkin added. This could serve as a model for outbreak response while simultaneously providing essential scientific evidence while simultaneously offering equitable treatment access.

STOMP findings mirror earlier results reported this year from an NIAID-cosponsored, randomized controlled trial testing tecovirimat among children and adults living in Democratic Republic of the Congo with Clade I Mpoxvirus infections.

NIAID-funded study, executed through the ACTG network. SIGA Technologies of New York provided tecovirimat for this trial. Through out this study, NIAID and STOMP investigators worked in close coordination with key partners like the CDC, FDA, study country health authorities, teams conducting other trials of tecovirimat studies as well as additional key partners involved with responding to MPOX infections. These consultations enabled research partners to come to efficient answers to scientific inquiries, reconcile evidence needs with compassionate use considerations, and offer up-to-date information for clinicians treating Clade II Mpox globally. UNITY, sponsored by ANRS Emerging Infectious Disease and using similar criteria as STOMP in Argentina, Brazil and Switzerland to evaluate tecovirimat, has also begun. Additional information for this trial can be found through ClinicalTrials.gov using NCT05597735 as its study ID.

NIAID is committed to supporting research to fill evidence gaps on medical countermeasures against pandemic threats such as MPOX. Their efforts include supporting networks like Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness Network; Antiviral Program for Pandemics; and Antiviral Drug Discovery Centers for Pathogens of Pandemic Concern that undertake research that leads to safe, effective vaccines, monoclonal antibodies, antivirals medicines against virus families with potential pandemic potential – collectively conducting discovery, basic, translational research that results in development of vaccines; monoclonal Antibodies for Pandemic Preparedness Network; Antiviral Program for Pandemics; Antiviral Program for Pandemics; Antiviral Program Pandemics; and Antiviral Drug Discovery Centers for Pandemic Concern to develop safe yet effective vaccines, monoclonals Antivirus Drug Discovery Centers Pathogens of Pandemic Concern antivirals medicines against virus families that pose pandemic potential threats.
Sources for allergy and infectious disease data include the National Institute of Allergy and Infectious Diseases.