The current Ebola outbreak is the most widespread epidemic of Ebola virus disease (EVD) in history and is currently ongoing in three West African countries. The Ebola virus has a high case mortality rate: in the three countries most affected by the outbreak — Guinea, Sierra Leone and Liberia — about 71% percent of the infected people have died. It began in Guinea in December 2013 and then spread to Liberia and Sierra Leone. A small outbreak of nineteen cases occurred in Nigeria and one case occurred in Senegal. The latter two countries were declared disease-free on 20 October 2014 after a 42 day waiting period.
Ebola is expected to infect 1.4 million people by January 2015. Pharmaceutical companies and governments are joining forces to urgently halt the current outbreak. As of 2nd November 2014, the World Health Organization (WHO) has reported a total of 13,042 suspected cases; the WHO believes that this substantially understates the magnitude of the outbreak with true figures numbering three times as many cases as have been reported. The assistant director-general of the WHO warned in mid-October that there could be as many as 10,000 new EVD cases per week by December 2014. Almost all of the cases have occurred in the three initial countries.
Prior to this current outbreak there had only been 2,418 cases in total. Scientists simply didn’t know enough about how this rare virus works in the human body, nor did they have access to enough patients to learn from and treat with experimental drugs. Given the small number of people who would have benefited from an Ebola cure before this outbreak, experts say big pharmaceutical companies could not see much of a commercial return for pursuing lengthy, costly drug research.
Cuts in government funding to the World Health Organisation have contributed to critical delays in responding to this Ebola outbreak which allowed the epidemic to spin out of control, disease experts say. The UK, US and other European governments reduced contributions to the organisation because of global austerity, and also failed to implement much-needed structural reforms, they said. The WHO needs urgent reform, if future global health crises are to be avoided.
Nevertheless, there are a few of experimental treatments out there. Ideally, these untested therapies would undergo years of randomized, controlled trials – first in animals, then in small groups of humans. But at this late stage in the current outbreak, with thousands of people suffering, medical ethicists say placebo groups in Ebola trials would be unfair. As long as there are certain standards for the trials, World Health Organization officials also agreed that using untested drugs on suffering Ebola patients is ethical.
In the absence of large-scale, clinical trials that can scientifically prove whether or not therapies are effective, all eyes are on the handful of cases that are so far serving as anecdotal evidence for the most promising Ebola treatments. Here is a summary of the drugs leading the race to find drugs to treat Ebola:
The Livestock Vaccine (VSV-EBOV)
This vaccine uses a virus found in livestock, modified to include part of the gene from the Ebola virus. VSV-EBOV was developed at the National Microbiology Laboratory in Winnipeg and is a cocktail of interferon-alpha, made by our immune system and three cloned antibodies. It’s licensed to NewLink Genetics of Iowa, which will have up to 12 million doses of the vaccine ready by April 2015. Human testing began in October 2014. Studies already undertaken in primates found that it prevents infection when given before exposure and increases survival chances when given after exposure. Each vial contains two doses of the vaccine and had been created for clinical trials before the headline-making outbreak.
The original roadmap had been for clinical trials to start early next year. In a paper last year, the lab reported that their combination therapy saved three out of four cynomolgus macaques and four of four rhesus macaques when given three days after infection with Ebola Zaire, the deadliest strain. Ordinarily, a stage I clinical trial would be used to establish dosing and safety and then it would proceed at a rather slow and expensive pace through the approval process to make sure it actually works before being used, but public outcry has led to calls for fast-tracking vaccines.
The Shot Vaccine (Unnamed Shot)
GSK acquired the vaccine after buying Swiss-based biotech company Okairos for 250 million euros ($319 million) last year. The GSK vaccine consists of a common cold virus, called an adenovirus, engineered to carry two genes of the Ebola virus. It works by attacking the Zaire species of Ebola, which is responsible for the current outbreak. Animal testing has shown that when the adenovirus infects cells the Ebola genes produce harmless proteins that stimulate the immune system to produce antibodies to Ebola. It is considered to be safe because it does not contain any infectious viral material – this means it cannot cause a person who is vaccinated to become infected with Ebola.
“Development of the vaccine candidate is progressing at an unprecedented rate, with first phase 1 safety trials with the vaccine candidate underway in the USA, UK and Mali, and further trials due to start in the coming weeks,” the firm said in a statement posted on its website.
“The thing that is going to have the biggest impact is what is happening to the trajectory of the epidemic curve. If you progress the current trends 2 months into the future are we still in an environment where you can even consider doing a trial?” Dr. Ripley Ballou ‒ Head of Ebola Vaccine Research, GSK
At the GSK vaccine research facility outside of Brussels, they are working to squeeze 10 years of trial activity into 12 months. The company said preliminary data from the trials was expected by the end of 2014 and that, if successful, the next phase, involving the vaccination of frontline healthcare workers in Sierra Leone, Guinea and Liberia, would begin in early 2015.
The Double Barrel (Unnamed Vaccine)
Johnson & Johnson
J & J is a little behind the other two, with trials of its vaccine due to start in January. Theirs a two shot solution. The vaccine targets the Zaire strain of the virus, and combines a candidate from Janssen, a J&J unit dedicated to finding treatments for unmet medical needs, with one from Danish biotech company Bavarian Nordic. The first gets patients’ immune systems ready for action, and the second increases their responsiveness. The shots in humans may be given at two week increments, though in animal trials the wait was two months.
$200m (£124m) has been pledged to accelerate the research programme, and it plans to manufacture one million doses over the course of the next year. J&J said 250,000 of these will be released for “broad application” in clinical trials by May.
J & J has invested $43m in Bavarian Nordic to help the much smaller company scale up its vaccine production. Volunteers in the US, Africa and Europe will be given the vaccine, which has already shown “promise” in animal testing. Bavarian Nordic’s Chief scientific officer Dr Stoffels, said the aim to produce over a million vaccines in the next few months was “within reach. We are committed to bringing our science, technology, innovation and resources to help prevent and treat this deadly disease”.
The Gene Patch (TKM-Ebola-Guinea)
Tekmira’s product targets the Ebola-Guinea virus variant, which is responsible for the worst outbreak on record that has hit hardest in Liberia, Sierra Leone and Guinea. It works by blocking the message that comes from the DNA of Ebola so it can no longer hijack the human host cell and multiply. This allows the immune system of the infected individual to defeat the virus.
Tekmira, of Vancouver, Canada has been working with the US Department of Defense and started human testing in early 2014. They had already shown encouraging results in primates, turning 100% fatality into 80% survival. Limited amounts of their drug will be available by December 2014. “In the long-term,” says the company, “this gene patch might be the most useful of all these drugs as it will be the most stable and portable and can be given both before and after exposure.”
Tekmira also produces a treatment called TKM-Ebola, which has been used on several patients, including an infected U.S. medical missionary who contracted the virus in Liberia. The man recovered after treatment with the drug and a “convalescent serum” made up of antibodies taken from the blood of a U.S. Ebola survivor.
The Small Molecule (Brincidofovir)
Recently the FDA gave permission for this antiviral “small molecule” drug from Chimerix, to be given to patients with Ebola. Dallas patient Thomas Eric Duncan used this drug but still died. Doctors Without Borders plans on trying it in West Africa ASAP without doing a double blind study.
The Flu Jab (Avigan)
An anti-flu vaccine made by Japan’s Fujifilm stops viral genes from reproducing. It may work the same way on Ebola. Some research papers report that Avigan shows also efficacy against the Ebola virus in animal testing with mice.
Avigan has already been administered as an emergency treatment to several EVD patients evacuated from West Africa to Europe. Fujifilm provided Avigan Tablets to these patients in response to requests from governments and medical organizations treating the evacuated patients following discussions with the Japanese government. A French nurse treated with the drug recovered from Ebola.
The Tobacco Vaccine (ZMapp)
ZMapp uses an approach called passive immunotherapy. Instead of having a vaccine stimulate the immune system to make antibodies that attack the virus, passive immunotherapy simply supplies the antibodies to the patients where they then directly and specifically react with the virus in a “lock and key” fashion, thus neutralizing it. For some infectious diseases, these antibodies are extracted from the blood of patients who have survived the infection and presumably have effective antibodies.
ZMapp instead consists of a combination of 3 monoclonal antibodies that are made by exposing mice to a key Ebola protein and harvesting their antibodies. Those antibodies are then genetically modified to make them more like human antibodies and therefore less likely to provoke an immune reaction if injected into people.
The gene for each antibody is then introduced into the leaves of genetically engineering tobacco plants using a system developed by Icon Genetics, a German company. The leaves then produce the antibody.
Scientists in Thailand believe they’ve found a new type of antibody that is effective against the virus. The team of doctors at Siriraj Hospital are confident that it will work and the side effects will be low, but it has not been tested in animals or humans and is at least a year away at least from being developed.
A doctor in Liberia has tried lamivudine, a drug used in HIV and Hepatitis, in 15 patients with Ebola; all but two survived. Compared with the 70% mortality rate in West Africa, those are good odds. The drug can cause liver problems and has other side effects, but the doctor said it has been worth it in light of the disease’s deadliness.