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SUNDAY SCIENCE: ‘THAT COULD BE A GAME CHANGER’: AN ANTIVIRAL PILL
GETS FIRST TEST FOR EBOLA PREVENTION  
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Kai Kupferschmidt
May 29, 2026
Science
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_ Researchers are preparing to launch an unprecedented trial to
protect people exposed to Ebola in the DRC and Uganda _

Health workers outside an Ebola isolation unit in Mongbwalu,
Democratic Republic of the Congo on 26 May., Michel Lunanga/Getty
Images

 

When the World Health Organization (WHO) announced on Thursday its
recommendations for treatments and preventive measures to test in the
current Ebola outbreak, a lot of the candidates were familiar:
vaccines in various stages of development (though none ready to test
are specific to the rare Ebola virus variant known as Bundibugyo
that’s currently spreading), and antivirals and monoclonal
antibodies for those who fall sick. But one thing is new: a trial for
a 10-day course of pills intended to protect people after they have
been exposed to Ebola.

Researchers and health officials hope the approach can slow the
outbreak, which has now caused more than 1000 suspected cases
including more than 200 deaths in the Democratic Republic of the Congo
(DRC) and Uganda. “Since we don't have vaccines, this is something
you can do immediately that could be effective”, says Ira Longini, a
biostatistician at the University of Florida.

The preventive strategy, known as post-exposure prophylaxis (PEP),
mirrors what has proved successful for other infectious diseases.
Here, researchers will test an experimental antiviral called
obeldesivir. It would be the first controlled trial to evaluate
antivirals as a preventive measure during an Ebola outbreak.

At the moment, direct contacts of Ebola patients get visited daily to
check for symptoms, but that’s it, says Armand Sprecher of Doctors
Without Borders. “All you’re doing every day is saying, ‘Are you
sick yet? Are you sick yet?’” Sprecher says. If obeldesivir works,
it would not only prevent cases and thus spread, but might also
facilitate contact tracing by motivating more contacts to come
forward, he says. “That could be a game changer.”

Gilead began to develop obeldesivir early in the COVID-19 pandemic as
an oral counterpart to its antiviral remdesivir, an intravenous drug
that was widely used against the novel coronavirus SARS-CoV-2.
Clinical trial results for remdesivir against Ebola viruses have been
mixed. It did not clearly reduce mortality among people with the Zaire
strain of Ebola in the PALM trial, conducted during a devastating
outbreak in the DRC that started in 2018. Still, some evidence
suggests it can help Ebola patients if given early enough after
infection.

The idea for the current prevention trial was also born from that same
outbreak. In 2019 Marie Jaspard, an infectious disease specialist at
the Sorbonne University, was working in Béni in the eastern DRC when
a health care worker asked how to help a woman who had been caring for
her ill husband at home and then learned he was infected with Ebola. A
vaccine for Ebola Zaire was available, but it would take several days
for its protection to kick in, too late for the woman. “The research
question came from this exact moment where I had to answer this
colleague,” Jaspard says. “To me there was clearly a gap in the
care.”

So Jaspard, with Congolese virologist Placide Mbala and other
researchers, started an emergency-use program offering one of two
experimental antibody drugs against Ebolaviruses, called mab114 and
REGN-E3B, to people who had had direct contact with symptomatic
patients. Both had just been shown in the PALM trial to reduce
mortality in patients infected with Ebola Zaire, but were not yet
approved as therapies. They might be even more powerful virus-fighters
if delivered before symptoms emerge, the researchers reasoned.

None of the 23 people who received one of the two drugs over the next
6 months got sick. But it is unclear how many infections would have
been expected in the group, so after the outbreak ended, Jaspard put
together a consortium, including the National Institute for Biomedical
Research in Kinshasa and the medical humanitarian organization ALIMA,
that designed a larger and more rigorous test—a trial called
EBO-PEP—to be ready to use in the next Ebola Zaire outbreak.

More recently, Jaspard and her colleagues updated the EBO-PEP protocol
to include another candidate: obeldesivir, which has the benefit of
being taken as a pill. Like remdesivir, it is transformed in the body
through a series of steps into the active molecule GS-443902, which
mimics the structure of ATP, a molecule viruses need in order to
replicate. “It’s like somebody sticking a piece of cardboard into
the photocopier, and it jams things up,” Sprecher says. But unlike
remdesivir, obeldesivir can be absorbed in the gut before it’s
turned into the active molecule.

Tests of obeldesivir as PEP in monkeys have been encouraging. Between
80% and 100% of animals survived when they received the treatment 24
hours after being injected with the Zaire and Sudan strains of Ebola,
or with the related Marburg virus. Without the drug, the animals
didn’t stand a chance, says virologist Thomas Geisbert of the
University of Texas Medical Branch, who led the studies. “They all
die, and they die quickly.” But, he adds, “Guess what, we didn’t
test [it against] Bundibugyo.”

Jaspard and her colleagues are now adapting the EBO-PEP protocol for
the current outbreak. They face some thorny issues, including what the
trial should offer people in the control group. The original trial
protocol, designed for an Ebola Zaire outbreak, gives all participants
the Zaire vaccine, randomizing them to vaccine-only or
vaccine-plus-antiviral groups. Some researchers think that even with
Bundibugyo, the Zaire vaccine is likely to have a short-term
protective effect because the vesicular stomatitis virus used to
deliver Ebola’s surface protein generally ramps up the immune
system. But in the current outbreak, WHO has discouraged trialing a
vaccine that is designed to protect against a different pathogen.

At a meeting of the trial consortium on Tuesday, Sprecher says Vasee
Moorthy from WHO’s Office of the Chief Scientist “made it clear
that it was not up for discussion.” The agency hasn’t publicly
shared its reasoning, but in an email Moorthy noted the limited data
on the effectiveness of existing vaccines against Bundibugyo.

“If we had data to support vaccination (and maybe we will get it at
some point) then we would be doing something for everyone. That would
be my preference,” Sprecher says. But he also points out that most
contacts of an infected person will never develop Ebola, meaning that
many of those receiving the drug would only experience the side
effects. It will be up to health authorities in the DRC and Uganda to
decide whether they accept a trial design where the control group only
gets placebo pills.

Another question is how best to distribute obeldesivir. Because family
members of an infected person might live in the same house but be
randomized to different arms of the study, researchers want to make
sure they don’t share or mix up their pills. With doses required
twice a day for 10 days, it’s not possible for health workers to
observe participants taking each pill. “The plan is to have a
community engagement team that will go to the houses of participants
every day and give them the drugs,” Jaspard says. “We will see if
it's feasible.” In Uganda this is not a problem, because contacts
are usually separated and taken to an isolation center for 21 days,
says Pauline Byakika-Kibwika, a researcher at Mbarara University of
Science and Technology, who along with Jaspard and Mbala is a
principal investigator of the study.

The study is meant to include only people at the highest risk of
developing Ebola, but it’s not easy to define that group. The team
has decided to focus on those who had contact with confirmed Ebola
patients with “wet” symptoms such as bleeding or vomiting, those
who had contact with the body of an Ebola victim, and those who got a
needle-stick injury while treating an infected patient. “I guess
that it's simple enough at this stage,” Jaspard says, “and we
worked a lot with the countries to make sure this is acceptable.”
Experience from previous work in the DRC suggests that there is
usually a ring of roughly 20 people who have had direct contact with a
patient, Longini says. He has made some calculations about how many
participants would be needed to prove whether the preventive strategy
works in the trial. If obeldesivir has a very strong protective
effect, that could be clear from just a few dozen rings in each of the
two arms, he says.

Nearly 7 years after her first attempt to test Ebola prevention drugs,
Jaspard is stunned by the sudden interest in the trial. “I've kept
this project for all these years, despite the fact that a lot of
people were saying it's not useful, you don't need to do this, go
away,” she says. Longini admits he did not think a PEP study was
crucial in Ebola until now. “It was not something I thought we'd
have to resort to,” he says. “I thought we would have the vaccines
ready when these things happen.”

doi: 10.1126/science.zjr657e

_KAI KUPFERSCHMIDT is a contributing correspondent
for Science magazine based in Berlin, Germany._

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* Science
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* Medicine
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* antiviral
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* Ebola
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* World Health Organization
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* prevention
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