A new study suggests the antiviral drug obeldesivir may be effective in curing Ebola Sudan infections, for which there are currently no approved vaccines or treatments.
Scientists at the University of Texas Medical Branch in Galveston tested the drug, made by Gilead, in primates, starting treatment 24 hours after the animals were given what should have been a lethal dose of Sudan ebolavirus by intramuscular injection. The five monkeys that were treated all survived; two control animals given a placebo succumbed to the disease.
The promise of this treatment is that obeldesivir is given in pill form — in this study in a regimen of one pill daily for 10 days. If the drug is shown to be effective in people and is approved, it would be the first treatment for any type of Ebola that is given orally. The only approved Ebola treatments — for the species of the virus known as Ebola Zaire — are monoclonal antibodies that are expensive to produce, require cold storage, and must be given intravenously.
“I think you could really, really control these outbreaks quicker if you have something like this,” said Tom Geisbert, a microbiologist and senior author of the paper, which was published Thursday in Science. “I think it can definitely be a game-changer.”
Geisbert said the window of time in which treatment must be started could turn out to be longer in people, especially in an outbreak setting. That’s because the monkeys were given very high doses of virus by injection, an approach that mirrors what might happen in a laboratory accident but does not reflect real-world transmission.
“It’s meant to mimic a worst-case scenario,” he said. “We did this at 24 hours. But you probably have a lot more time in humans.”
Armand Sprecher, an expert in Ebola and other so-called filoviruses who works for Doctors Without Borders, agreed that the drug could profoundly change Ebola responses, noting obeldesivir can be stored at room temperature, is relatively inexpensive to manufacture, and — based on work in cell culture — appears to be active against all known species of Ebola and the related virus, Marburg. There are currently no approved treatments or vaccines that are effective against multiple filoviruses.
“All of those things are great advantages,” Sprecher told STAT in an interview. He and Geisbert stressed, though, that the in vitro findings that suggest the drug could be a pan-ebolavirus therapy will need to be tested in animal models and eventually in people.
There are several species of ebolaviruses. Ebola Zaire is the most common cause of outbreaks, followed by Ebola Sudan. But there are long stretches between outbreaks of the latter, making it difficult to test drugs or vaccines for this version of the virus in the field. The most recent Ebola Sudan outbreak occurred in 2022, in Uganda.
Gilead said it was encouraged by the results of the UTMB research. The company provided the drug for the study and was involved in the design of the trial. But the study was funded by the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health.
“Gilead is evaluating next steps for the path forward in these neglected viruses with high unmet medical need, including potential partnerships to help progress research for this important potential indication,” a company spokesperson said via email.
Gilead had been testing obeldesivir as a possible therapy for Covid-19, conducting a Phase 3 trial that was completed last year. But in February, the company revealed that the trial failed to meet its primary endpoint, potentially because of when in the pandemic the drug was tested.
“Essentially because of the way things have evolved, the standard-risk population is now better able to fight Covid-19 without antiviral therapy. This made it more difficult for obeldesivir to show a benefit compared to placebo,” CEO Daniel O’Day said in a statement issued with Gilead’s fourth-quarter earnings report. “We know that the world needs to be equipped for other viruses, and the broad antiviral activity of obeldesivir shown preclinically means it has potential for other viral infections.”
Obeldesivir is related to remdesivir, an antiviral drug that was tested in the landmark PALM trial, during the massive 2018-2020 Ebola Zaire outbreak in the Democratic Republic of the Congo. The trial tested four drugs against each other; no placebo was used. All of the drugs appeared to reduce the risk of death, but only the two most efficacious have since been licensed: Inmazeb, a cocktail of three antibodies made by Regeneron Pharmaceuticals, and Ebanga, a single monoclonal developed by NIAID and commercialized by Ridgeback Biotherapeutics.
The PALM trial tested the drugs in people who were already sick with Ebola. But the hope for obeldesivir is that it could be given to people who have been exposed to deadly Ebola viruses before they become ill, potentially cutting short the disease process before people become so sick they need to be cared for in isolation.
“If you are giving people this drug while the virus is still getting its act together in the lymphoid tissue, maybe you can inhibit the virus enough to prevent disease and the patient doesn’t get sick,” Sprecher said.
That could fundamentally alter the challenging dynamics that often arise during Ebola and Marburg outbreaks. Frightened people watch as the sick from their community are taken away to be treated in isolation. Historically most died in the treatment units and families were not even given back the bodies of their loved ones for burial. The bodies of people who die from filovirus infection are teeming with viruses and ritual burial ceremonies can be super-spreader events.
The fatality rates of recent Ebola Zaire outbreaks have been lowered through use of Merck’s Ervebo, and the two approved antivirals, Inmazeb and Ebanga. But that hasn’t fundamentally changed the dynamics of outbreaks; the distrust of the outsiders who come to try to extinguish Ebola’s spread remains, Sprecher said. During the 2018-2020 outbreak in DRC — the second-largest on record — a treatment unit was razed and several responders were killed.
The beauty of having a drug in pill form is that responders could use it in combination with an Ebola vaccine, if available, to effectively blanket a community where transmission was happening. (The only currently approved vaccine, Ervebo, only protects against Ebola Zaire. A recently published study conducted by Doctors Without Borders showed the vaccine improves the survival chances of people who are vaccinated when they are incubating the disease but are not yet symptomatic.)
“Vaccinate everybody — contacts, contacts of contacts, and anybody in the damn village — and then you can give the obeldesivir to anybody who has a remote risk of having been infected,” Sprecher said.