Scientists are hopeful about several medications that have shown promise in preliminary studies against the virus responsible for the current deadly Ebola outbreak, with clinical testing expected to start soon, reports The New York Times.
One of the experts in the Democratic Republic of Congo, South Africa’s Dr Salim Abdool Karim – who leads the Africa Centres for Disease Control and Prevention experts group on the outbreak – said he was “pretty optimistic” that one of the drugs to be trialled will work, and that if it does, “it’s quite cheap, and generics are widely available”.
In a hastily assembled treatment centre in Rwampara, DRC, Dr Papys Lame and his colleagues rehydrate patients who arrive in paroxysms of diarrhoea 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 Lame, the Ebola response co-ordinator 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 specifically targeting Bundibugyo virus, the species causing the current outbreak in East Africa. More than 700 people have been infected so far, and nearly 200 have died. Scientists are searching intensely to find drugs that might work.
Why are there no treatments?
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 WHO recommends two drugs as treatments for Ebola virus.
But just because 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 studies yielded promising results. But scientists did not push the research further, because before now there had only been two small outbreaks of Bundibugyo. 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 this virus. The WHO has compiled a list of candidates for immediate trials, while 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 a monoclonal antibody, a molecule that locks on to the surface of a virus and prevents it from getting into cells.
Other drugs – antivirals – stop viruses from replicating once they are inside cells. Some grab on to 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, also proved safe for people to take.
In a few cases, doctors are already using MBP-134 to treat Bundibugyo infections. American physician Dr Peter Stafford received it after he became infected in the DRC and was flown to Europe for treatment last month. He also received remdesivir, the antiviral drug used in the past for other diseases, including Covid. It has shown promise in early studies on Bundibugyo.
Stafford was discharged from Charité Hospital in Berlin on 6 June. 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 prioritise which drugs to test in trials, the WHO gathered experts to review preliminary studies. On 28 May, 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, organise 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.
Rojek and her colleagues began a trial of remdesivir in Rwanda in 2024, during an outbreak of Marburg, and plan to combine these results with a new trial in which remdesivir will be tested against Bundibugyo.
While the trial design may accelerate results, the current outbreak presents a host of challenges, she warned. It is taking place in an active conflict zone, and treatment centres are only now being established. 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.
“Only a limited number of candidates is available for clinical trials, so if these fail, there are no ready alternatives in the pipeline,” said Carmen Pérez Casas, head of pandemic preparedness at global health agency Unitaid, which is trying to arrange funds for early clinical testing of possible therapeutics.
Rojek’s trial will test two of the treatments on the WHO 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.
The CDC’s Abdool Karim said: “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 the DRC and Uganda are tracing 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 also hope to test an antiviral that may lower the risk that contacts develop Ebola disease, in a post-exposure prophylaxis strategy.
The trial will test a 10-day course of obeldesivir – 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 Galverston’s 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,” 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.
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 caring for them could receive the protective pills. If any of these drugs work, will East Africans get them?
The family of Stafford, the American physician treated for the virus, were given MBP-134 in Berlin as post-exposure prophylaxis. None developed Ebola. As they were leaving the hospital, Stafford expressed his gratitude but added that he hoped all patients in the DRC could receive the same level of care he and his family did.
Questions of access have haunted treatments tested in previous Ebola outbreaks. 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 the DRC, a trial funded largely by the US National Institutes of Health tested four monoclonal antibodies treatments. Two cut deaths in patients by as much as 50%. 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 the DRC.
Two companies, Regeneron and Ridgeback Biotherapeutics, ended up holding the intellectual property. Neither has yet registered either drug in any of the countries where Ebola outbreaks occur.
Ridegeback said it has provided one of the drugs, ansuvimab, free in four Ebola outbreaks in the DRC under a special access protocol, though declined to say how many patients had received it.
But most of the supply of both drugs is held in the USA’s national security stockpile.
SA pledges more support
Meanwhile, President Cyril Ramaphosa has said South Africa will increase its share in the pledge to fight Ebola to $13.5m – up from the previous $5m that was announced in May, reports News24.
Ramaphosa, in his capacity as the African Union Champion on pandemic prevention, preparedness, and response, addressed a high-level virtual meeting of heads of state, government, and partners on the outbreak this week, and said the increased pledge was his country’s commitment to “solidarity and sovereignty for the people of this continent”.
On Tuesday, he called on all leaders “to maintain or increase their pledges, and all those who made pledges at the last meeting to convert them in full into cash, medical countermeasures or technical assistance”.
He added that with no vaccine or antiviral, “every day that transmission continues unchecked, the human cost rises”, urging them to accelerate investment in local manufacturing, strengthen the African Medicines Agency, and operationalise the African Pooled Procurement Mechanism.
African manufacturers must have predictable markets, the President said, and African countries must have access to lifesaving products.
“I call upon African financial institutions, development banks, philanthropies, and the African private sector to join governments in this effort, and for our international partners to continue to stand with Africa in a spirit of solidarity and mutual responsibility.”
See more from MedicalBrief archives:
World experts call for urgent response, saying Ebola was preventable
Responders struggle to contain Ebola as outbreak surges
WHO wants more funds to fight DRC Ebola epidemic