The antiviral Tecovirimat is safe, but it did not improve the resolution of Clade I Mpox in the Democratic Republic of the Congo.
A study co-sponsored by the National Institutes of Health looked at tecovirimat in a country where smallpox is common.
The antiviral medicine tecovirimat did not shorten the duration of mpox lesions in children and adults with clade I mpox in the Democratic Republic of the Congo (DRC), according to an initial analysis of data from a randomized, placebo-controlled trial. However, the study’s 1.7% overall death among registrants, regardless of whether they took the medicine or not, was significantly lower than the mpox mortality of 3.6% or higher recorded in all cases in the DRC. This demonstrates that people with mpox can have better outcomes if they are hospitalized and receive high-quality supportive care. The trial is sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID) and co-led by the Democratic Republic of the Congo’s Institut National de Recherche Biomédicale (INRB). Additional analysis and detailed data will be disseminated via scientific channels.
“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, M.P.H. “We remain committed to developing safe and effective interventions, including treatments and vaccines, that can ease the devastating mpox burden in Central Africa and address the milder form of the virus that is circulating globally.”
Mpox has been present in West, Central, and East Africa for decades, with the first human case reported in 1970. Two varieties of the mumps virus have been identified. This trial focused on Clade I, which is endemic in Central Africa and can cause serious sickness. Clade II, which is indigenous to West Africa, causes a milder disease. A clade II subtype virus produced a worldwide mpox outbreak in 2022. People with weakened immune systems, children, and pregnant women are more vulnerable to severe mpox, regardless of the virus lineage.
Reports of clade I mpox are becoming more common in Central African countries, particularly the DRC. According to a recent report from the Centers for Disease Control and Prevention (CDC), 67% of suspected DRC mpox cases and 78% of suspected mpox deaths occurred in people aged 15 and under. Tecovirimat (link is external), also known as TPOXX, was developed and approved by the Food and Drug Administration to treat smallpox (link is external), a virus that is closely related to but far more serious than mpox. However, the drug’s safety and efficacy as a mpox treatment have yet to be established.
It is presently accessible for mpox therapy in the United States as part of a separate NIAID-sponsored experiment known as STOMP, as well as through a CDC expanded access Investigational New Drug (EA-IND) request process. Tecovirimat is approved in Europe and the United Kingdom to treat smallpox, mpox, and other conditions.
In October 2022, the NIAID and INRB initiated the PALM007 trial to investigate the safety and efficacy of tecovirimat for mpox therapy in both adults and children. At two study sites in the Democratic Republic of the Congo, 597 persons with laboratory-confirmed mpox participated. Participants in the study were randomly assigned to receive tecovirimat or a placebo and admitted to a hospital for at least 14 days, where they were intensively monitored for safety and mpox lesion resolution. All participants received supportive care, which included feeding, hydration, and treatment for subsequent infections.
Tecovirimat was well tolerated, with no significant drug-related side effects. Overall, mortality was lower, and lesions healed faster than expected regardless of whether they got tecovirimat or a placebo. Trial participants are being advised of the preliminary results and offered the opportunity to engage in an ongoing extension trial that will provide additional supportive medical care. Additional analyses are planned to better understand the study’s findings, including whether there were any significant differences in clinical outcomes based on days of symptoms prior to enrollment, severity of clinical disease, participant characteristics, or the genetic variant of mpox being treated.
“This study provided much-needed evidence to guide the mpox response in Central Africa,” said co-principal investigator Jean-Jacques Muyembe-Tamfum, M.D., Ph.D., 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 in managing mpox-related disease.”
“The PALM007 study demonstrated the importance and value of testing investigational mpox treatments through robust clinical trials in the DRC’s endemic setting,” stated Lori Dodd, Ph.D., NIAID’s DRC PALM project lead. “We will continue to examine trial data to decide whether future studies of tecovirimat in patient subgroups are necessary.
The PALM007 trial is led by co-principal investigators Professor Muyembe-Tamfum and Placide Mbala, M.D., Ph.D., operations manager of the PALM clinical research partnership and head of the Epidemiology and Global Health Department and the Pathogen Genomic Laboratory at INRB. Protocol co-chairs are NIAID’s Veronique Nussenblatt, M.D., and Olivier Tshiani, M.D., of Leidos Biomedical Research. The trial was carried out in Tunda (Maniema province) and Kole (Sankuru province), with assistance from Congolese personnel, the Mitchell Group, and the NIH’s Frederick National Laboratory for Cancer Research. The United States Centers for Disease Control and Prevention (CDC), the Institute of Tropical Medicine Antwerp (ITM), the relief organization Alliance for International Medical Action (ALIMA), and the World Health Organization (WHO) are among the institutions that have collaborated.
Logistics and operations for supplies, travel, and regional security were supported by the US Embassy in the DRC and U.S. CDC officials stationed in the DRC. SIGA Technologies, Inc. of New York provided tecovirimat for the study.
The “Pamoja Tulinde Maisha” or “PALM” clinical research alliance was formed in response to the 2018 Ebola outbreak in the Democratic Republic of the Congo. The partnership has continued as a multilateral clinical research initiative that includes NIAID, the DRC Ministry of Health, INRB, and INRB’s partners.
NIAID and the INRB would like to thank the remarkable team of persons who carried out this study in remote regions of the DRC, the members of the independent study Data and Safety Monitoring Board, and, most significantly, the study participants and their families. For more information about PALM007, go to ClinicalTrials.gov and enter the study number NCT05559099.
“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,” according to Dr. Marrazzo.
The multinational STOMP trial is looking into the safety and efficacy of tecovirimat in treating clade II mpox. For additional information on the STOMP trial, go to ClinicalTrials.gov and enter the study ID NCT05534984. Further research by UNITY, financed by ANRS Emerging Infectious Disease, is assessing tecovirimat in Argentina, Brazil, and Switzerland using a design similar to STOMP. More information about the UNITY study can be obtained at ClinicalTrials.gov with the identifier NCT05597735. Both trials will continue to enroll individuals, and they will work closely together.
NIAID conducts and supports research at the National Institutes of Health, across the United States, and across the world to better understand the causes of infectious and immune-mediated diseases, as well as to create better methods of prevention, diagnosis, and treatment. The NIAID website features news releases, info sheets, and other NIAID-related materials.
Regarding the National Institutes of Health (NIH): The National Institutes of Health (NIH), the country’s medical research organization, consists of 27 institutes and centers and is part of the United States Department of Health and Human Services. The National Institutes of Health (NIH) is the principal government institution that conducts and supports fundamental, clinical, and translational medical research, as well as studies the causes, treatments, and cures for both common and rare diseases. For more information on the NIH and its activities, go to www.nih.gov.
