The World Health Organization (WHO) recently declared a global health emergency over the mpox (formerly monkeypox) outbreak in Africa due to an increase in the number of cases in the Democratic Republic of Congo (DRC), spread to neighboring countries, and the identification of a strain with increased virulence.
Recently, a randomized, placebo-controlled trial was conducted in the DRC to test the effectiveness of the antiviral drug tecovirimat against the monkeypox virus. The findings suggest that the drug did not reduce the duration of mpox lesions among children and adults with clade I mpox, based on an initial analysis of data.
“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 Jeanne Marrazzo, MD, director of the National Institute of Allergy and Infectious Disease (NIAID).
Notably, the study’s 1.7% overall mortality among enrollees, regardless of whether they received the drug or not, was much lower than the mpox mortality of 3.6% or higher reported among all cases in the DRC. This suggests that better outcomes among people with mpox can be achieved when they are hospitalized and provided high-quality supportive care.
“This study delivered urgently needed evidence to guide the mpox response in Central Africa,” said Jean-Jacques Muyembe-Tamfum, MD, PhD, director-general of INRB and professor of microbiology at Kinshasa University Medical School in Kinshasa, DRC. “Although not what we had hoped for, the results show that study clinicians provided exceptional supportive care to all participants, which is a testament to the knowledge and skill that Congolese clinicians have acquired on managing mpox-related disease.”
Mpox has occurred in West, Central, and East Africa for decades, with the first human case identified in 1970. Two types of the virus that causes mpox have been identified. Clade I, studied in this trial, is endemic in Central Africa and can cause severe illness. Clade II, endemic in West Africa, tends to result in milder illness. A clade II subtype virus caused a global mpox outbreak in 2022. People with compromised immune systems, children, and people who are pregnant are especially vulnerable to severe mpox regardless of the virus clade.
Reports of clade I mpox are increasing in Central African countries, particularly in the DRC. A recent report from the CDC indicated that 67% of suspected DRC mpox cases and 78% of suspected mpox deaths have occurred in people aged 15 years and younger.
Tecovirimat, also known as TPOXX, was initially developed and approved by the FDA to treat smallpox, but the drug’s safety and efficacy as an mpox treatment have not been established. It is currently available for mpox treatment in the United States as part of a separate NIAID-sponsored trial, STOMP, and through a CDC expanded access Investigational New Drug (EA-IND) request process. Tecovirimat is authorized in Europe and the United Kingdom for the treatment of smallpox, mpox, and other indications.
In October 2022, NIAID and INRB launched the PALM007 trial (NCT05559099) to examine the safety and efficacy of tecovirimat for mpox treatment 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, where they were monitored closely for safety and resolution of mpox lesions. All participants received supportive care including nutrition, hydration, and treatment for secondary infections.
Tecovirimat was well-tolerated with no drug-related serious adverse events. Overall, mortality was lower, and lesions resolved faster than anticipated regardless of whether participants received tecovirimat or placebo.
“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, PhD, NIAID’s Pamoja Tulinde Maisha (PALM) project lead for the DRC. “We’ll continue to evaluate the trial data to determine whether additional studies of tecovirimat in patient subgroups are warranted.”
The PALM clinical research partnership was established in response to the 2018 Ebola outbreak in DRC. The collaboration has continued as a multilateral clinical research program composed of NIAID, the DRC Ministry of Health, INRB, and INRB’s partners.
“Given the differences in populations affected by the two mpox clades, the types of clinical disease that are appearing, and the ongoing spread of both clades, it’s very important that we continue with the STOMP trial and other related studies, so that we can develop treatments that benefit all people with mpox,” said Marrazzo.
The international STOMP trial (NCT05534984) is examining the safety and efficacy of tecovirimat against clade II mpox. An additional study, UNITY (NCT05597735), sponsored by ANRS Emerging Infectious Disease, is evaluating tecovirimat with a similar study design to STOMP in Argentina, Brazil, and Switzerland.
