Antiviral drug tecovirimat fails to cure Mpox in Democratic Republic of Congo

The World Health Organization (WHO) recently declared a global health emergency in relation to the outbreak of Mpox (formerly monkeypox) in Africa due to an increase in the number of cases in the Democratic Republic of Congo (DRC), spread to neighbouring countries and the identification of a strain with increased virulence.

Recently, a randomized, placebo-controlled trial was conducted in the Democratic Republic of Congo to test the efficacy of the antiviral drug tecovirimat against monkeypox virus. The results suggest that the drug did not shorten the duration of Mpox lesions in children and adults with clade I Mpox, based on an initial data analysis.

“These results are disappointing, but they provide us with important information and underscore the need to identify other therapeutic candidates for Mpox as we continue research into the use of tecovirimat in other populations with Mpox,” said Dr. Jeanne Marrazzo, Director of the National Institute of Allergy and Infectious Disease (NIAID).

Most notably, the overall mortality of 1.7% among study participants, whether or not they received the drug, was much lower than the Mpox mortality of 3.6% or more reported for all cases in the Democratic Republic of Congo. This suggests that better outcomes may be achieved in people with Mpox if they are hospitalized and receive high-quality supportive care.

“This study provided much-needed insights to guide the response to Mpox 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 the results did not meet our expectations, they demonstrate that study physicians provided exceptionally supportive care to all participants, which is a testament to the knowledge and skills Congolese physicians have acquired in managing Mpox-related diseases.”

Mpox has been present in West, Central, and East Africa for decades. The first human case was identified in 1970. Two types of the virus that causes Mpox have been identified. Clade I, examined in this study, is endemic to Central Africa and can cause severe disease. Clade II, endemic to West Africa, tends to cause milder disease. A virus of the Clade II subtype caused a global Mpox outbreak in 2022. People with weakened immune systems, children, and pregnant women are particularly susceptible to severe Mpox, regardless of the virus clade.

Reporting of Group I Mpox is increasing in Central African countries, particularly in the Democratic Republic of Congo. A recent CDC report stated that 67% of suspected Mpox cases and 78% of suspected Mpox deaths in the Democratic Republic of Congo occurred in persons 15 years of age and younger.

Tecovirimat, also known as TPOXX, was originally developed and approved by the FDA to treat smallpox, but the drug's safety and effectiveness for treating smallpox have not yet been established. It is currently available in the United States to treat smallpox under a separate NIAID-sponsored trial, STOMP, and through an expanded CDC Investigational New Drug (EA-IND) application process. Tecovirimat is approved in Europe and the United Kingdom to treat smallpox, smallpox, and other indications.

In October 2022, NIAID and INRB launched the PALM007 trial (NCT05559099) to evaluate the safety and efficacy of tecovirimat for the treatment of Mpox in adults and children. The trial enrolled 597 people with laboratory-confirmed Mpox at two sites in the Democratic Republic of Congo. Study participants were randomly assigned to receive tecovirimat or placebo and hospitalized for at least 14 days, where they were closely monitored for safety and healing of Mpox lesions. All participants received supportive care, including nutrition, hydration, and treatment of secondary infections.

Tecovirimat was well tolerated and no serious side effects occurred. Overall, mortality was lower and lesions healed faster than expected, regardless of whether participants received tecovirimat or placebo.

“The PALM007 trial demonstrated the importance and value of testing experimental Mpox treatments through robust clinical trials in the endemic setting of the Democratic Republic of Congo,” said Lori Dodd, PhD, NIAID's Pamoja Tulinde Maisha (PALM) Project Director for the Democratic Republic of Congo. “We will 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 the Democratic Republic of Congo. The collaboration continues as a multilateral clinical research program implemented by NIAID, the Democratic Republic of Congo Ministry of Health, INRB, and INRB partners.

“Given the differences in the populations affected by the two Mpox clades, the clinical disease types that occur, and the progressive spread of both clades, it is very important that we continue the STOMP trial and other related studies so that we can develop treatments that benefit all people with Mpox,” Marrazzo said.

The international STOMP trial (NCT05534984) is investigating the safety and efficacy of tecovirimat against clade II mpox. Another trial, UNITY (NCT05597735), sponsored by ANRS Emerging Infectious Disease, is investigating tecovirimat using a similar study design to STOMP in Argentina, Brazil, and Switzerland.