Hopes for drug against monkeypox virus widespread in Africa dashed

According to the U.S. National Institutes of Health (NIH), the drug tecovirimat did not speed up the recovery of people infected with a worrisome strain of monkeypox virus in a clinical trial in the Democratic Republic of Congo (DRC). The strain, called Clade I, has spread in Africa and is considered more deadly than the strain that caused a global monkeypox outbreak that began in 2022 and is known as Clade II.

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Tecovirimat, an antiviral agent, is widely used to treat smallpox, although there is limited clinical evidence that it relieves symptoms. The drug was originally developed to treat smallpox caused by a related orthopoxvirus.

“These are certainly not the ideal results we were all hoping for,” says Jason Kindrachuck, a virologist at the University of Manitoba in Winnipeg, Canada.

The spread of Clade I in the Democratic Republic of Congo and other African countries prompted the World Health Organization (WHO) to declare an international health emergency – the highest level of alert – on August 14. One day earlier, the Africa Centers for Disease Control and Prevention (Africa CDC) had declared a public health emergency for the first time due to the outbreak.

And yesterday, Sweden reported the first case of a person infected with a Clade I variant, called Clade Ib. Scientists had reported in April that this variant can be transmitted through sexual contact between people. Before last year, Clade I was thought to be transmitted through household contact and through contact with infected wild animals.

Disappointing results

During the study, launched by the NIH's National Institute of Allergy and Infectious Diseases (NIAID) and the DRC's National Institute of Biomedical Research, people infected with Clade I received either tecovirimat or a placebo. According to the NIH, which announced initial results on August 15, the antiviral did not shorten the duration of Mpox symptoms compared to placebo.

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Mpox, the disease caused by the monkeypox virus, can cause fluid-filled lesions, fever, headache, and in severe cases, death.

Importantly, however, the mortality rate among study participants, regardless of whether they received tecovirimat or placebo, was lower than the overall mortality rate for all types of MPOX typically reported in the Democratic Republic of Congo: 1.7% versus 3.6%.

This may be due to the care participants received during the study. The 597 people who took part in the study were hospitalized for at least 14 days. During this time, they received nutritional support, adequate hydration, treatment of any other infections or illnesses they may have had, including malaria, and psychosocial support, among other things.

“The level of care was very high,” says Lori Dodd, a biostatistician at NIAID in Bethesda, Maryland, and principal investigator of the study. Maintaining this high quality of care outside of a clinical trial can be challenging, she adds, “so the team will work to translate this model of care to people with MPOX recovering in outpatient settings and in resource-limited settings.”

Hope for certain groups

Tecovirimat's maker, New York City-based SIGA Technologies, said in a press release that study participants who were treated with the drug early on, as well as those with severe disease, saw “significant improvement.” But full data has not yet been published. They are currently being analyzed and a manuscript is being prepared for submission to a peer-reviewed journal, Dodd says.

“We are all excited about the trial, especially to see if there is a group that could be targeted, especially people with HIV,” says Piero Olliaro, an infectious disease specialist at the University of Oxford in the UK. He adds that the prognosis tends to be worse in people with advanced HIV infection and in those who become infected with the monkeypox virus.¹.

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It is not yet clear whether the study results can be extrapolated to clade Ib. “We do not currently know much about clade Ib and need to study the clinical presentation and outcomes in more detail to decide whether new clinical trials are needed,” says Olliaro.

Although these preliminary results for tecovirimat are disappointing, Kindrachuck said, they indicate that “we can actually accelerate recovery by providing funding to the Democratic Republic of Congo and other countries to support patients with clade I pox.”

Nicaise Ndembi, a virologist at the Africa CDC in Addis Ababa, says the findings do not change the response plan for the current outbreaks, which includes increased surveillance, more laboratory testing, strategic distribution of the limited vaccine doses available and negotiations to procure additional doses. But he says they underscore the fact that an appropriate standard of care is critical to reducing mortality associated with MPOX.

Although there is a vaccine against Mpox, produced by biotechnology company Bavarian Nordic in Hellerup, Denmark, it is still largely unavailable in African countries. However, Bavarian's CEO Paul Chaplin told STAT News that the European Union has ordered 175,000 doses to be donated to Africa CDC.

With additional reporting by Max Kozlov.