The drug tecovirimat represented, along with vaccines, one of the main hopes in the fight against Mpox. At least until now. This antiviral, also known as “Tpoxx” or “tecovirimat SIGA”, was the only treatment available to fight Mpox, regardless of its variant. It was supposed to reduce or even prevent the spread of the virus in the body after contamination. Specialists saw it as a weapon of choice in the current epidemic of Mpox “clade 1”, a variant that appeared last year in the Democratic Republic of Congo (DRC) and has since spread to Central Africa. A phenomenon sufficiently worrying for the World Health Organization to declare an “international health emergency” on August 14.
Unfortunately, tecovirimat does not appear to be effective against Mpox “clade 1” and “clade 1b”. This is indicated by the preliminary results of the “Palm007” trial, conducted in the DRC since 2022 by the National Institutes of Health (NIH), the National Institutes of Health in the United States, and whose results have just been made public.
Tecovirimat was originally developed and approved to treat smallpox, a related but eradicated virus. Researchers hoped that tecovirimat would also be effective against Mpox. This hope was fueled in particular by the fact that smallpox vaccines are 80 to 85% effective against Mpox thanks to a phenomenon of cross-reactivity. The antiviral was therefore approved in January 2022 by the European Medicines Agency (EMA) for the treatment of Mpox, under “exceptional circumstances”, while the epidemic of the “clade 2b” variant of Mpox was raging around the world.
In France, The High Council for Public Health (HCSP) had even issued an opinion on May 24, 2022 considering that, “for patients suffering from a severe form of the disease”, tecovirimat was “the treatment to use as first-line treatment”. This recommendation is still online on the Ministry of Health website.. Haste? In the emergency context, the authorisations were in any case given before all the evidence of effectiveness had been gathered.
“No reduction in the duration of injuries”
The “Palm007” trial, currently being conducted in the DRC, aims to assess the benefits of the various treatments available, including tecovirimat. The researchers therefore conducted a “randomized placebo-controlled study”, the ultimate in scientific proof. They recruited 597 people with Mpox in the DRC and randomly assigned them to two groups. The first received tecovirimat, the other a placebo. All patients, however, benefited from a 14-day hospitalization during which they received “high-quality supportive care”, including antibiotics in the event of superinfection of the lesions caused by Mpox, treatments to reduce fever and pain, as well as appropriate nutrition and hydration.
The preliminary results are clear: “Tecovirimat was well tolerated and did not cause any serious adverse drug reactions.” […]but the antiviral did not reduce the duration of lesions in children and adults with ‘clade 1’ Mpox in the Democratic Republic of Congo (DRC),” the NIH said. in a press release published on August 15but went relatively unnoticed.
Appropriate care reduces mortality by more than half
While the researchers considered these results “disappointing,” they did point out some good news: their trial showed that high-quality care reduced mortality among infected people by more than half. “The overall mortality of 1.7% among participants, whether they received tecovirimat or not, was much lower than the mortality of 3.6% or more reported elsewhere in the DRC. This shows that better outcomes can be achieved among people with Mpox when they are hospitalized and receive high-quality supportive care,” the NIH press release continued.
“While not what we had hoped for, the results show that study physicians provided exceptional supportive care to all participants, which is a testament to the knowledge and skills that Congolese physicians have gained in managing Mpox-related illnesses,” added Dr. Jean-Jacques Muyembe-Tamfum, professor of microbiology at the University of Kinshasa School of Medicine in the DRC and co-author of the study, in the NIH statement.
“The mortality rate of Mpox is therefore largely linked to a lack of access to care and medication in remote and poor regions of the DRC,” analyses Dr. Eric D’Ortenzio, a Mpox specialist and epidemiologist at ANRS MIE, an autonomous agency of Inserm specializing in emerging infectious diseases. We can therefore hope that the mortality rate of people affected in developed countries is not higher than this percentage.
The preliminary results of the trial also serve to alert the international community to the need for continued research to identify or develop new treatments. “One of the current challenges is indeed to find new antivirals,” confirms Dr. D’Ortenzio.
Efficacy against “clade 2” not yet known
In the meantime, health authorities hope that tecovirimat will prove effective against “clade 2”, which continues to rage mainly in West Africa, but also against its “clade 2b” variant which caused the 2022 epidemic. The “Unity” clinical trial, currently being conducted by ANRS MIE, aims to answer these questions. The first centers participating in this trial have been opened in Brazil and Switzerland, and the first patients have been included in Brazil since March 3, 2023. Other countries where cases related to this strain of Mpox are still being reported, particularly in Latin America, will join the study.
The trial has two arms. The first is randomized, placebo-controlled and double-blind. The patients included are therefore randomly divided into two groups, one receiving tecovirimat and the other a placebo, and neither the caregivers nor the patients know who is receiving the treatment. The second arm is open and non-randomized and allows for compassionate use of the drug: all patients receive tecovirimat. This arm is intended for people with severe manifestations of the disease, including significant pain, or at risk of severe form. The results should be known within a few months. But whether they are positive or not, it will be necessary in any case to find an effective treatment, in addition to the vaccine, against Mpox “clade 1b”.
.