William A. Fischer II, MD, Director of Emerging Pathogens at UNC’s Institute for Global Health and Infectious Diseases and Joe Eron, MD, UNC Chief of Infectious Diseases and chair of the ACTG, co-authored a study that found tecovirimat used to treat mpox does not shorten time to lesion resolution, reduce pain, or speed viral clearance in adults. Published today in the New England Journal of Medicine, the results call for a renewed focus on new antivirals and combination strategies.
Chapel Hill, N.C. — An international, randomized, double‑blind, placebo‑controlled phase 3 study—the largest of its kind for mpox—found that tecovirimat did not improve clinical outcomes for adults with clade II mpox compared with placebo, while demonstrating a similar safety profile. Results of the STOMP/A5418 trial, published in the New England Journal of Medicine underscore both the urgent need for alternative therapeutics and the critical importance of randomized trials during public health emergencies.
This Phase 3 study randomized 412 participants (344 with laboratory‑confirmed mpox), to receive either tecovirimat or a matching placebo for 14 days. Randomization was stratified by early versus later symptom onset and by the presence of severe pain. Participants had active skin or mucosal lesions and self‑reported daily symptoms, pain scores, and lesion status through Day 29, with confirmatory clinical assessments at scheduled visits. Biospecimens—including lesion swabs, oral and rectal swabs, and blood samples—were collected at multiple time points to assess viral DNA clearance. The primary endpoint was time to clinical resolution of all lesions, and key secondary endpoints included pain reduction, complete lesion healing, and virologic response.
Conducted across seven countries at 49 sites, the phase 3 study showed that tecovirimat did not shorten the time to lesion resolution, reduce pain, or speed viral clearance compared with placebo. These results align with interim findings released in December 2024, which led the trial’s independent Data and Safety Monitoring Board to halt further enrollment due to statistical futility.
“In the midst of a global public health emergency, the ACTG team rapidly conducted this randomized controlled trial to deliver a clear answer for patients and clinicians,” said William A. Fischer II, MD, associate professor of pulmonary and critical care medicine at the UNC School of Medicine, and director of emerging pathogens research at the UNC Institute for Global Health and Infectious Diseases. “These findings advance our understanding of mpox and help the field refocus efforts on identifying safe, effective and accessible treatment strategies, particularly for people at highest risk of severe disease.”
Although the trial did not demonstrate efficacy, tecovirimat demonstrated a favorable safety profile, with no major safety concerns identified—an important confirmation as thousands of patients worldwide have already received the drug under expanded access protocols.
“The STOMP trial provides essential evidence at a critical time and demonstrates why randomized controlled trials are an indispensable part of outbreak response,” said Joe Eron, MD, chief of infectious diseases and chair of the ACTG network. “But now we must keep going to find safe and effective treatment for people as this virus continues to circulate globally.”
The study’s conclusions are expected to influence clinical practice and public health guidance worldwide. With mpox still causing outbreaks in multiple regions, researchers emphasize that developing and evaluating new antiviral candidates remains a top priority.
About the Institute for Global Health and Infectious Diseases
Established in 2007, the UNC Institute for Global Health & Infectious Diseases at the UNC School of Medicine started over 30 years ago with infectious disease physician researchers studying HIV in China and Malawi. Through the years, our work has expanded to include emerging pathogens, cancer, women’s health and vector-borne disease like malaria–shaping policy through evidence-based research around the world. At UNC-Chapel Hill, the Institute facilitates research excellence while nurturing emerging scientists to advance patient care and practice, addressing the most important global health issues of our time–through research, training and service.
About the ACTG
Founded in 1987, the ACTG (Advancing Clinical Therapies Globally) is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. Dr. Joe Eron, a researcher with the UNC Institute for Global Health and Infectious Diseases, chairs the ACTG network, which now houses the ACTG operation center at the University of North Carolina at Chapel Hill.