Ebola horror hastens use of test drugs
In need of a cure. Ebola test vaccines raise hopes and worries
DAKAR, 21 August 2014 (IRIN) - Ebola’s devastation in West Africa has catapulted experimental drugs from labs to patients and shaken up vaccine development, which was hitherto patchy as outbreaks of the virus have tended to be spasmodic and geographically limited.
“There is no market for Ebola vaccines,” Marie-Paule Kieny, World Health Organization (WHO) assistant director-general, told IRIN. “Outside of an outbreak, who would want to get vaccinated against Ebola? Nobody. Therefore the market is inexistent more or less. So there was not that much investment into developing that. Nevertheless, they were carrying forward.”
For common diseases like malaria, WHO uses a tool known as a Rainbow Table to track vaccine research and trials. The table maps out potential malaria vaccines and their various trial stages with a view to creating a vaccine against the disease that kills some 627,000 people every year.
When Ebola struck, there was no such map available to guide health workers and experts through the maze of possible ways to battle the fever. “There is no Rainbow Table for Ebola, because until very recently there was not enough happening to justify a Rainbow Table,” Kieny said.
Experimental treatments and ethical dilemmas
As Ebola spread from Guinea to neighbouring Liberia and Sierra Leone, there were a handful of vaccines and treatments that had shown promise in animal studies, but they were not immediately rolled out to Ebola patients in West Africa.
The rising death toll - 1,350 people in Guinea, Liberia, Sierra Leone and Nigeria as of 18 August - has increased the incentives to try experimental drugs which carry unknown risks. The availability of such drugs is also very limited.
On 11 August, WHO convened a panel to “assess the ethical implications for clinical decision-making of the potential use of unregistered interventions”. It agreed that it would be “ethical” to offer experimental drugs under the “particular circumstances” of this Ebola outbreak.
There is also controversy over who the priority recipients of such drugs should be. California-based Mapp Biopharmaceutical Inc. which developed the ZMapp vaccine said recently it had exhausted
its available supplies. Administration of the vaccine also posed a real dilemma recently to a team of Médecins Sans Frontières (MSF) physicians treating Sheikh Umar Khan, Sierra Leone’s lead Ebola doctor, who died of the disease on 29 July.
MSF said it faced a “medical decision that was much more difficult than usual” on whether to give Khan ZMapp. The drug was later delivered to Liberia and given to two US aid workers who had contracted Ebola. They were flown back home and have been reported to be in better health. However, a Spanish priest being treated with the drug died days after being repatriated from Liberia.
Other than Mapp Biopharmaceutical Inc., the Canadian government has said it will donate up to a 1,000 doses of an experimental vaccine known as VSV-EBOV to WHO. “The vaccine, VSV-EBOV, has never been tested in humans, but has shown promise in animal research,” Canada’s public health agency said in a statement
The US Food & Drug Administration this month lifted what had been a “full clinical hold” placed on the TKM-Ebola drug developed by Canadian pharmaceutical firm Tekmira, and changed it to a “partial clinical hold” which allows the potential use of the drug on patients.
Chris Garabedian, CEO of Massachusetts-based Sarepta Therapeutics, told IRIN they contacted US regulatory officials to alert them that they have enough doses of their experimental drug, AVI-7537, to treat a couple of dozen people.
Garabedian said the drug has been tested in Ebola-infected rhesus monkeys with a success rate of 60-80 percent. It has also been tested in healthy humans for safety concerns, but not in infected humans. So far the company has not had any requests for the drug.
“This year there was much more initiative into this development and many, many stakeholders that have… been trying to see how they can push more quickly through the development process. But even so, it’s very difficult to compress in a matter of days a process which usually takes years,” said WHO’s Kieny.
But MSF, which has some 600 doctors in West Africa battling the outbreak, insisted that while it is “keen for its patients to benefit from any treatment that shows promise”, other control measures should be bolstered.
“Combating the outbreak requires a massive scaling up of all the known measures such as community mobilization, education, effective contact-tracing, early presentation of suspected Ebola patients at appropriately equipped treatment centres, training and equipping health workers, and effective coordination of the response,” an MSF spokeswoman said.
Breaking new ground
“There are attempts to see how these vaccines can be made available, and under which conditions, to healthcare workers and other populations at risk when there is a suspicion of high-risk exposure, so this is really completely new. This is breaking ground to see how this can proceed,” Kieny said. “It is not possible to take something which has not been tested in any humans so far and suddenly deploy this in thousands of doses.”
Patients must sign waivers stating they understand the risks. “Otherwise there would be no hope of developing anything, because we won’t know if these drugs will work. We don’t even know whether they can cause harm instead of doing good, because they are completely experimental,” Kieny explained.
Jeanine Thomas, a US-based patients’ advocate who sat on the WHO panel on experimental Ebola treatment, said she knows first-hand what it is like to believe you are dying and the necessity for treatment. Thomas fell ill with MRSA, a bacterial infection resistant to several antibiotics, but her physicians failed to tell her what she was suffering from.
“It’s a horrifying experience, and you’re screaming inside for someone to help… So I certainly hope that if there had been a drug and I was in the situation of a family member I would have said, ‘OK try this’,” she said. “All of those options need to be on the table.”
Slow drug development
Although Ebola has only erupted in Africa, Western companies have conducted research with state funding, especially after the US government classified Ebola as a bioterrorism agent.
“Back in the 70s when Ebola was first identified, people thought it was a one-off [outbreak],” said Eleanor Riley, professor of immunology at the London School of Hygiene & Tropical Medicine. “Since then there were occasional small outbreaks and it wasn’t seen as a priority.”
That changed after the 11 September attacks and bioterrorism worries. “At that point the US started investing in biodefence, developing vaccines not because they thought there was going to be a global epidemic, but because they thought someone might use them to kill American troops. So they have been gradually ticking over [with] this but not urgently,” said Riley.
Much of the ongoing research in the US is government-funded. In 2010, Sarepta Therapeutics was designated to receive up to US$291 million from the Department of Defence for its research into cures for the Ebola and Marburg viruses. Funding for Ebola was cancelled in 2012 due to federal budget cutbacks.
With Western companies doing the research on a drug that could potentially only be administered to Africans living far away, there are risks that using these experimental drugs could appear as if Africans are being used as guinea pigs, experts say.
“It is very important that these drugs and vaccines are tested concurrently in the countries where they have been produced and in Africa, so that both sides share the same responsibility and the same risk,” said Kieny.