A recent clinical trial conducted in the Democratic Republic of the Congo (DRC) has revealed that tecovirimat, an antiviral drug, did not significantly improve the resolution of mpox lesions in patients infected with the clade I variant. The PALM007 trial, sponsored by the National Institutes of Health (NIH) and co-led by the DRC’s Institut National de Recherche Biomédicale (INRB), aimed to assess the safety and efficacy of tecovirimat in treating mpox in a region where the disease is endemic.
The study enrolled 597 adults and children with laboratory-confirmed mpox across two sites in the DRC. Participants were randomized to receive either tecovirimat or a placebo, alongside comprehensive supportive care, including nutrition, hydration, and treatment for secondary infections. Although the drug was found to be safe and well-tolerated, initial data analysis indicated that it did not reduce the duration of mpox lesions.
Unexpectedly Low Mortality Rate
Interestingly, the trial reported an overall mortality rate of 1.7% among enrollees, regardless of whether they received tecovirimat or the placebo. This figure is notably lower than the mpox mortality rate of 3.6% or higher previously reported in the DRC. According to NIAID Director Jeanne Marrazzo, M.D., M.P.H., these findings emphasize that improved outcomes in mpox cases can be achieved through hospitalization and high-quality supportive care.
Ongoing Research and Future Directions
Despite the disappointing primary outcome, researchers plan to conduct further analyses to explore potential differences in clinical outcomes based on factors such as the duration of symptoms before enrollment, disease severity, patient characteristics, and the specific genetic variant of mpox being treated. These additional analyses may provide insights into specific patient subgroups that could potentially benefit from tecovirimat.
"These findings are disappointing, but they give us essential information and reinforce the need to identify other therapeutic candidates for mpox while we continue research on tecovirimat use in other populations with mpox," said Dr. Marrazzo.
Tecovirimat's Role in Mpox Treatment
Tecovirimat, also known as TPOXX, was initially developed and approved by the FDA for the treatment of smallpox. While it is authorized in Europe and the United Kingdom for treating mpox, its efficacy against mpox has not been definitively established. In the United States, tecovirimat is available for mpox treatment through a NIAID-sponsored trial (STOMP) and a CDC expanded access program.
Importance of Clinical Trials in Endemic Settings
Co-principal investigator Jean-Jacques Muyembe-Tamfum, M.D., Ph.D., director-general of INRB, emphasized the significance of conducting clinical trials in mpox-endemic regions like the DRC. "The PALM007 study demonstrated the importance and value of testing investigational mpox treatments through robust clinical trials in the DRC’s endemic setting," said Lori Dodd, Ph.D., NIAID’s PALM project lead for the DRC.
The PALM007 trial is part of the "Pamoja Tulinde Maisha" (PALM) clinical research partnership, established in response to the 2018 Ebola outbreak in the DRC. This collaboration underscores the ongoing commitment to developing effective interventions for infectious diseases in Central Africa.
