An initial analysis of a clinical study showed that the antiviral tecovirimat used for the treatment of mpox did not reduce the duration of lesions caused by the disease in children and adults infected with clade 1, the most lethal variant and responsible for the current outbreak in the Democratic Republic of the Congo (DRC). The preliminary results were released in a press release made by the National Institutes of Health (NIH) — a conglomerate of health institutes in the United States — on Thursday (15).
On the other hand, the analysis observed a lower mortality (1.7%) among study participants regardless of whether they received the drug or not, compared with the mortality from mpox among all cases reported in the DRC (3.6%). This means that better health outcomes can be achieved when people with mpox are hospitalized and receive high-quality supportive care.
“These findings are disappointing, but they provide us with essential information and reinforce the need to identify other therapeutic candidates for mpox as we continue research into the use of tecovirimat in other populations with mpox,” said Jeanne Marrazzo, director of the National Institute of Allergy and Infectious Diseases (NIAID), in a statement released by the NIH.
“We remain committed to developing safe and effective interventions, including treatments and vaccines, that can alleviate the devastating burden of mpox in Central Africa and address the milder form of the virus that is circulating globally,” he added.
How the study was done and what are the next steps
The recently released initial analyses are part of the PALM007 study, launched in October 2022 by NIAID and the DRC’s Institut National de Recherche Biomédicale (INRB). The study aimed to examine the efficacy and safety of tecovirimat for the treatment of mpox in adults and children. The study enrolled 597 people with laboratory-confirmed mpox at two sites in the DRC.
Study participants were randomly assigned to receive tecovirimat or placebo and were admitted to a hospital for at least 14 days. There, they were closely monitored for safety and resolution of mpox lesions. According to the study, all participants received supportive care, including nutrition, hydration, and treatment for secondary infections.
Although preliminary analysis did not observe an improvement in the duration of lesions caused by the disease in participants with clade 1 of the virus, tecovirimat was well tolerated, with no serious adverse events related to the drug.
Additional analyses are planned to better understand the results observed in the study, including whether there were any significant differences in clinical outcomes by days of symptoms prior to enrollment, clinical disease severity, participant characteristics, or the mpox genetic variant being treated.
“This study has provided urgently needed evidence to guide the response to mpox in Central Africa,” says co-principal investigator Jean-Jacques Muyembe-Tamfum, director general of INRB and professor of microbiology at the University of Kinshasa Medical School in Kinshasa, DRC.
“Although not what we expected, the results show that the study clinicians provided exceptional supportive care to all participants, which is a testament to the knowledge and skill that Congolese clinicians have acquired in managing mpox-related diseases,” he adds.
What is tecovirimat?
The antiviral drug tecovirimat was developed to treat smallpox, but was licensed in 2022 by the European Medicines Agency (EMA) to treat mpox, based on data from studies in animals and humans. In the same year, the National Health Surveillance Agency (Anvisa) exceptionally and temporarily waived the registration requirement for the drug imported by the Ministry of Health, due to the outbreak that was occurring at the time and that affected Brazil.
In animal studies, tecovirimat has been shown to reduce the chance of death from orthopoxvirus infections, such as the MPOX virus, when given early in the course of the disease. In people, a case series of individuals infected with the virus, which included a patient treated with tecovirimat, suggests that the drug may shorten the duration of the disease and viral spread. The results were published in the Lancet in 2022.
According to the US Centers for Disease Control and Prevention (CDC), tecovirimat may be considered for treatment in people infected with the MPOX virus with severe disease, such as hemorrhagic cases, large lesions that are found, sepsis, inflammation of the brain (encephalitis) and other conditions that require hospitalization.
The use of the antiviral may also be indicated for individuals with one or more complications, such as secondary bacterial infection, gastroenteritis with severe nausea and vomiting, diarrhea or dehydration, or other comorbidities. WHO recommends that the use of tecovirimat be monitored in a clinical research context with prospective data collection.
