In a hastily assembled Ebola treatment center in Rwampara, Democratic Republic of Congo, Dr. Papys Lame and his colleagues rehydrate patients who arrive in paroxysms of diarrhea and vomiting, transfuse those who bleed uncontrollably from their noses and mouths, and provide oxygen for those in respiratory distress. They monitor patients’ hearts and blood pressure, and treat their intense pain.
It’s a significant improvement from outbreaks that Dr. Lame, the Ebola response coordinator in Congo for the Alliance for International Medical Action, worked on even five years ago. “Today we have more options, and more people survive,” he said.
But they are still missing something crucial: a treatment that specifically targets Bundibugyo virus, the species that has caused the current outbreak in East Africa. At least 695 people have been infected so far, and 138 have died. Scientists are searching intensely to find drugs that might work.
Why are there no treatments for Bundibugyo virus?
Over the past 50 years, most outbreaks of Ebola disease were caused by a different species of virus, known as Ebola virus. Based on clinical trials, the World Health Organization recommends two drugs as treatments for Ebola virus.
But just because scientists know that a drug works against one virus doesn’t mean that it works against the other. Their evolutionary differences are just too great.
After Bundibugyo virus emerged in 2007, scientists ran preliminary experiments with cells and animals to see if any drugs could stop it. Some of those studies yielded promising results. But scientists did not push the research further, because before now there had only been two small outbreaks of Bundibugyo virus. With limited funds to perform the expensive research, they had to choose their battles.
“If you were a betting person, you would not have bet on Bundibugyo to cause something large,” said Thomas Geisbert, a virologist at the University of Texas Medical Branch at Galveston. “And, of course, we’re all wrong now.”
Now scientists are rushing to pinpoint drugs to test in clinical trials against Bundibugyo virus. The W.H.O. has put together a list of candidates for immediate trials. Scientists are also hunting for other compounds that might be worth testing.
What would a drug need to do to work?
One type of drug that works against viruses is known as a monoclonal antibody. This molecule locks onto the surface of a virus and prevents it from getting into cells.
Other drugs, known as antivirals, stop viruses from replicating once they have gotten inside cells. Some grab onto viral proteins, causing them to shut down. The disabled proteins can no longer do essential jobs like making new virus genes.
A monoclonal antibody called MBP-134 has proved effective at stopping Bundibugyo infections in monkeys, and in early clinical trials for Ebola virus, it has also proved safe for people to take.
In a few cases, doctors are already using MBP-134 to treat Bundibugyo infections. An American physician, Dr. Peter Stafford, received it after he became infected in Congo and was flown to Europe for treatment last month. He also received remdesivir, an antiviral drug that’s been used in the past for other diseases, including Covid. It has shown promise in early studies on Bundibugyo virus.
Dr. Stafford was discharged from Charité Hospital in Berlin on June 6. It’s impossible to know for certain if MBP-134 or remdesivir helped save his life. The only way to gain that kind of knowledge is through carefully designed clinical trials, comparing people who get experimental drugs with those who get only supportive care.
Clinical trials may start soon.
To prioritize which drugs to test in trials, the W.H.O. brought together experts to review preliminary studies. On May 28, they recommended moving MBP-134 and remdesivir into clinical trials, along with another monoclonal antibody, maftivimab, and another antiviral, obeldesivir.
An ordinary clinical trial can take many months or even years. It takes time to get regulatory approval, organize the logistics and find enough patients to treat. Many past Ebola outbreaks ended before clinical trials could even begin.
The Bundibugyo outbreak could be different, said Dr. Amanda Rojek, an associate professor of health emergencies at the University of Oxford and a veteran of Ebola response. She and other researchers have been developing a new kind of clinical trial that makes it possible to test a single drug in multiple outbreaks caused by different viruses.
Dr. Rojek and her colleagues began a trial of remdesivir in Rwanda in 2024, during an outbreak of Marburg, another species of virus that causes a lethal disease much like Ebola. Dr. Rojek plans to combine these results with a new trial in which remdesivir will be tested against Bundibugyo virus.
While the trial design may speed up results, the current outbreak presents a host of challenges, she warned. It is taking place in an active conflict zone, and treatment centers are only now getting set up. And there is limited infrastructure to support clinical trials.
What treatments will be tested?
Given the scope of the need for treatments, there are frustratingly few good candidates for scientists to test.
“There are only a limited number of candidates available for clinical trials, meaning that if these fail, there are no ready alternatives in the pipeline,” said Carmen Pérez Casas, the head of pandemic preparedness at the global health agency Unitaid, which is trying to arrange funds for early clinical testing of possible therapeutics.
Dr. Rojek’s trial will test two of the treatments on the W.H.O. priority list. Some patients will receive MBP-134, while others will receive MBP-134 plus remdesivir. “We think there might be a combination effect between some of these agents,” she said.
The trial is in the final stages of regulatory approval, she said.
“I’m pretty optimistic that remdesivir may work,” said Dr. Salim Abdool Karim, who is in Congo and leads the Africa Centres for Disease Control and Prevention experts group on the outbreak. “It will be quite quick to show efficacy, because we have the patients there in the hospital. And if remdesivir does work, it’s quite a cheap drug, and generics are widely available.”
Are there drugs that can prevent people from getting sick in the first place?
Possibly.
Public health workers in Congo and Uganda are tracking down people who have had contact with patients and could be infected. For now, the contacts have to wait in isolation to see if they develop symptoms.
Researchers hope to test an antiviral that may lower the risk that contacts develop Ebola disease — a strategy known as post-exposure prophylaxis.
The trial will test a 10-day course of obeldesivir. The drug is essentially a cheap, oral form of remdesivir.
“This is the potential game-changer,” said Dr. Armand Sprecher, an epidemiologist and emergency physician with Doctors Without Borders who has worked on half a dozen Ebola outbreaks. “In somebody who is incubating illness, you could effectively cure them before they become sick. And it also means that they are not in the community shedding virus.”
Promising hints of obeldesivir’s effectiveness emerged from a study published last year by Dr. Geisbert and his colleagues. They gave monkeys obeldesivir starting just 24 hours after infection with Ebola virus — long before they would normally start showing symptoms.
“They were completely protected,” Dr. Geisbert said. “I mean, they didn’t even get sick.”
They also tested the drug against another species of virus that causes Ebola disease, called Sudan virus, and against Marburg. In all three cases, obeldesivir protected the animals.
But before the current outbreak, the scientists had not yet tested it on monkeys infected with Bundibugyo virus.
For pre-exposure prophylaxis to work, a health system has to be effectively tracing contacts. An effective drug would give those directing the outbreak response something to offer people, an incentive for sick people to go into isolation wards, if they know the family members who were caring for them could receive the protective pills.
If any of these drugs work, will East Africans get them?
The family members of Dr. Stafford, the American physician treated for the virus, were given MBP-134 in Berlin as post-exposure prophylaxis. None developed Ebola disease. As they were leaving the hospital, Dr. Stafford expressed his gratitude but added that he hoped all patients in Congo could receive the same level of care he and his family did.
Questions of access have haunted treatments tested in previous Ebola outbreaks. Dr. Rojek called post-trial access a critical issue and said it was “being worked through at the moment” for the therapeutics that might be tested in this outbreak.
In 2019, during an Ebola outbreak in Congo, a trial funded largely by the U.S. National Institutes of Health tested four monoclonal antibodies treatments. Two of the drugs cut deaths in patients by as much as 50 percent. One of them was developed from the blood of a Congolese Ebola survivor.
And yet, despite the public funding and the local origin of the treatments, there was no guarantee that the promising drugs would be supplied in Congo. Two companies, Regeneron and Ridgeback Biotherapeutics, ended up holding the intellectual property. Neither registered either drug in any of the countries where Ebola outbreaks occur.
Instead, the U.S. government bought the entire supply of both drugs for its own national security stockpile.
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