A recent study sponsored by the National Institutes of Health (NIH) and conducted in partnership with the Democratic Republic of the Congo’s (DRC) Institut National de Recherche Biomédicale (INRB) has found that the antiviral drug tecovirimat does not reduce the duration of mpox lesions in children and adults with clade I mpox. This conclusion comes from an initial analysis of data from a well-organised, randomised, placebo-controlled trial.

Despite this, the study has a positive takeaway: the overall mortality rate among participants was significantly lower at 1.7%, compared to the typical 3.6% or higher mortality rate reported among mpox cases in the DRC. This suggests that hospitalisation and high-quality supportive care can greatly improve outcomes for mpox patients.

An expert from NIAID expressed disappointment over the findings but emphasised their importance. The expert highlighted the need to identify other treatment options for mpox while continuing research on tecovirimat’s use in different populations. The commitment to developing safe and effective treatments and vaccines remains strong, aiming to ease the severe mpox burden in Central Africa and address milder forms circulating globally.

Mpox, also known as monkeypox, has been a health concern in West, Central, and East Africa for decades, with the first human case reported in 1970. There are two types of mpox virus: Clade I, which causes severe illness and is endemic to Central Africa, and Clade II, which usually causes milder illness and is endemic to West Africa. The Clade II subtype caused a global mpox outbreak in 2022. Vulnerable groups include immunocompromised individuals, children, and pregnant women, who are particularly at risk of severe mpox regardless of the virus type.

Reports indicate a rising number of clade I mpox cases in Central African countries, especially in the DRC. A recent report from the Centers for Disease Control and Prevention (CDC) noted that 67% of suspected DRC mpox cases and 78% of suspected mpox deaths occurred in individuals aged 15 years and younger.

Tecovirimat, also known as TPOXX, was initially developed and approved by the Food and Drug Administration (FDA) to treat smallpox—a more serious virus related to mpox. However, its safety and efficacy as an mpox treatment are still unconfirmed. In the United States, tecovirimat is available for mpox treatment through another NIAID-sponsored trial called STOMP and a CDC expanded access Investigational New Drug (EA-IND) request process. Tecovirimat is also authorised in Europe and the United Kingdom for treating smallpox, mpox, and other conditions.

In October 2022, NIAID and INRB launched the PALM007 trial to test tecovirimat’s safety and effectiveness for treating mpox in adults and children. The study enrolled 597 participants with confirmed mpox at two sites in the DRC. Participants were randomly assigned to receive either tecovirimat or a placebo and were hospitalised for at least 14 days for close monitoring. All participants received supportive care such as nutrition, hydration, and treatment for secondary infections.

The study found that tecovirimat was well-tolerated with no serious adverse events linked to the drug. Mortality was lower than expected, and lesions healed faster than anticipated regardless of whether participants received tecovirimat or placebo. Participants have been informed of these initial results and offered the chance to join an ongoing extension study providing further medical care. Additional analyses will be conducted to understand the outcomes better, including potential differences based on symptom duration before enrolment, disease severity, participant characteristics, or genetic variants of mpox being treated.

A co-leader of the study remarked that although the results were not as hoped, they highlight the excellent supportive care provided by Congolese clinicians. This underscores the knowledge and skill acquired by Congolese healthcare providers in managing mpox-related diseases.

Another expert involved in the PALM project for the DRC stressed the importance of testing investigational mpox treatments through robust clinical trials in endemic settings like the DRC. The trial data will continue to be evaluated to determine if further studies of tecovirimat in specific patient subgroups are needed.

Given the varying populations affected by the two mpox clades, differences in clinical disease manifestations, and ongoing spread of both clades, continuing with trials such as STOMP is crucial to develop treatments benefiting all mpox patients.