Hopes dashed for drug aimed at monkeypox virus spreading in Africa

The drug tecovirimat did not accelerate recovery for people in a clinical trial in the Democratic Republic of the Congo (DRC) who were infected with a concerning type of monkeypox virus, according to the US National Institutes of Health (NIH). The viral type, called clade I, has been spreading across Africa and is thought to be more lethal than the one that caused a global mpox outbreak that began in 2022, known as clade II.

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Tecovirimat, an antiviral drug, is used to treat mpox, despite there being limited clinical evidence that it resolves symptoms. The drug was originally developed to treat smallpox, which is caused by a related virus; both are members of the Orthopoxvirus genus.
“These are certainly not the ideal results that 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 DRC and other countries in Africa prompted the World Health Organization (WHO) to declare a public health emergency of international concern — its highest level of alert — on 14 August. A day earlier, the Africa Centres for Disease Control and Prevention (Africa CDC), based in Addis Ababa, declared its first-ever public-health emergency over the outbreak.
And yesterday, Sweden reported its first case of a person infected with a strain of clade I, called clade Ib, that scientists reported in April as being able to spread more easily between people, by means including sexual contact1. Before last year, clade I was thought to transmit mainly through household contact and through contact with infected wild animals.
During the trial, launched by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, and the DRC’s National Institute of Biomedical Research in Kinshasa, people infected with clade I were given either tecovirimat or a placebo pill. According to the NIH, which announced early results on 15 August, the antiviral did not reduce the duration of mpox symptoms compared with the placebo.

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Mpox, the disease caused by the monkeypox virus, can cause fluid-filled skin lesions, fever, headache and, in severe cases, death.
Significantly, however, the study participants’ mortality rate, regardless of whether they received tecovirimat or placebo, was lower than the overall mortality rate for any type of mpox reported in the DRC: 1.7% versus 3.6%.
This could be because of the care that the participants received during the trial. The 597 people enrolled were hospitalized for at least 14 days, and during this period they received, among other things, nutritional support; proper hydration; treatment for other infections or diseases they had, including malaria; and psychosocial support.
“The level of care was very high,” says Lori Dodd, a biostatistician at the NIAID and a project leader for the trial. Maintaining that high quality of care outside a clinical trial could be challenging, she adds, “so the team will be working on how to translate that care model for people with mpox who are recovering on an outpatient basis and in resource-limited settings”.
The maker of tecovirimat, SIGA Technologies, based in New York City, suggested in a press release that trial participants who had received early treatment with the drug and those who had severe disease had shown a “meaningful improvement”. But the full data have not been released. They are being analysed, and a manuscript is being prepared for submission to a peer-reviewed journal, Dodd says.
“We are all eager to see the paper, in particular to see if there is any group that could be selectively targeted for treatment, especially people with HIV,” says Piero Olliaro, an infectious-disease specialist at the University of Oxford, UK, adding that outcomes for people with advanced HIV who get infected with the monkeypox virus are often poor2.

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It’s not yet clear whether the trial results can be extrapolated to clade Ib. “We don’t know a lot about clade Ib for the time being, and we need more investigations into the clinical presentation and outcomes to inform whether new clinical trials are required,” Olliaro says.
Although the preliminary results for tecovirimat are disappointing, Kindrachuck says, they do point to the fact that “if we get resources into the DRC and beyond for support for patients with clade I mpox, we can actually increase recovery”.
Nicaise Ndembi, a virologist at the Africa CDC in Addis Ababa, says that the results do not change the response plan to the current outbreaks, which includes enhancing surveillance, increasing laboratory testing, strategic distribution of the limited vaccine doses available and negotiating the acquisition of more doses. But he says that the findings highlight the fact that an appropriate standard of care is crucial to reducing mortality related to mpox.
Although a vaccine against mpox, made by the biotechnology firm Bavarian Nordic in Hellerup, Denmark, exists, it is largely unavailable in African countries. However, Bavarian’s chief executive, Paul Chaplin, has reported to STAT News that the European Union has placed an order for 175,000 doses to be donated to the Africa CDC.