Hopes raised for Ebola breakthrough

All 18 rhesus macaques made a complete recovery, in contrast to three other untreated monkeys that quickly fell seriously ill and died.

ZMapp is a blend of three laboratory-made antibodies designed to neutralise the virus.

Two US doctors given the drug after they were infected with Ebola while working in Liberia subsequently recovered.

But it is not known whether they were saved by the drug or just lucky. About 45% of those infected in the current outbreak have survived without treatment.

At least two other patients treated with ZMapp have died, possibly because help got to them too late.

The new research, published in a special report on Nature journal’s website, provides hard evidence that the drug works and can be highly effective.

A team of scientists led by Dr Gary Kobinger, from the Public Health Agency of Canada, wrote: “ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use ...

“We hope that initial safety testing in humans will be undertaken soon, preferably within the next few months, to enable the compassionate use of ZMapp as soon as possible.”

The news follows a warning from the World Health Organisation (WHO) that the Ebola outbreak in West Africa could eventually claim more than 20,000 victims.

Latest figures show 1,552 deaths from the 3,069 cases reported so far.

Ebola, belonging to the family of “filoviruses”, ranks alongside Marburg virus as one of the world’s deadliest infections. Fatality rates in previous outbreaks have been as high as 90%.

It kills by overwhelming the immune system and sending the body into shock as blood pressure drops to dangerous levels.

Currently there are is no approved vaccine or post-exposure treatment. Management of the Ebola outbreak in Africa has been confined to palliative care and physical attempts to prevent transmission.

The development of ZMapp and its success in treating advanced stages of Ebola infection was described as a “monumental achievement” by Professor Thomas Geisbert, from the University of Texas, writing in Nature.

He added: “The next crucial step will be to formally assess its safety and effectiveness. Testing the latter is clearly difficult, because intentional infection of human subjects in clinical trials is not possible.”

The treated monkeys were exposed to a lethal level of Ebola virus before receiving three doses of ZMapp starting three, four and five days after infection.

The treatment reversed Ebola symptoms including excessive bleeding, rashes, and liver damage.

Three weeks after they were infected, no trace of the virus could be detected in the animals’ blood.

Untreated monkeys all succumbed to the virus by day eight after infection.

One drawback of the research was that it used a version of the virus different from the Guinea strain responsible for the current outbreak, which was not available at the time.

But the scientists went on to show that ZMapp blocks replication of the Guinea strain in laboratory tests.

Dr Alain Kohl, from the Medical Research Council/University of Glasgow Centre for Virus Research, said: “What needs to be done next is assess against how many strains and species of the virus it can act. Clinical trials in humans are not possible so some questions will go unanswered. At present too few people have received the drug to allow conclusions about efficacy and treatment timings, though in emergency situations it is at least one potentially useful option.”

David Evans, Professor of Virology at the University of Warwick, said: “All animals survived and had undetectable viral loads 21 days post-infection. This is an extremely encouraging result for a virus which has an incubation period of two to 21 days in humans and for which no vaccine exists.

“These results do not prove that the healthcare workers who received ZMapp and recovered did so due to the therapy. Others who also received ZMapp succumbed to the virus.

“Distinguishing between correlation and causation will require analysis of the clinical data on viral loads before and after therapy was administered. Nevertheless, the results are encouraging.”

Professor Martin Hibberd, from the London School of Hygiene & Tropical Medicine, said: “This looks to be a very well designed study with better than expected results, which give great hope for future clinical trials.

“I hope the team can receive sufficient funding to undertake these clinical trials straight away as this is by far the most advanced potential treatment option available to my knowledge.”

The Belgian scientist who discovered Ebola in 1976 while investigating reports of a terrifying new disease in Zaire – now the Democratic Republic of Congo - said it was vital to start clinical trials of ZMapp.

Professor Peter Piot, now director of the London School of Hygiene & Tropical Medicine, also spoke of his shock at the scale of the latest outbreak.

“This well designed trial in non-human primates provides the most convincing evidence to date that ZMapp may be an effective treatment of Ebola infection in humans,” he said. “It is now critical that human trials start as soon as possible.”

He added: “The resurgence of Ebola serves as a reminder of the importance of investing in health systems and infrastructure.

“This terrible disease is controllable with proper hygiene practices which all too often are not in place. We must work to find ways to alleviate symptoms and save lives with new treatments but at the same time we must act to prevent the spread of the disease.

“I never thought that 40 years after I encountered the first Ebola outbreak, this disease would still be taking lives on such a devastating scale.”

Dr Kobinger believes safety data paving the way to ZMapp’s approval as a treatment for Ebola could be available within a year.

“It could be as fast as the summer of 2015,” he said, speaking at a press briefing.

Meanwhile, the drug could still be used as it had already on compassionate grounds, despite being unlicensed.

It remains to be seen how quickly production of the drug can be geared up to meet future demand.

ZMapp, developed by US biotech company Mapp Biopharmaceutical Inc, is manufactured in the leaves of genetically modified tobacco plants.

Potentially the process could yield 20 to 40 doses per month, said Dr Kobinger.

Evidence suggests that effective treatment with ZMapp requires three doses of 15 milligrams per kilogram of body weight.

Currently, supplies of the drug are very limited. Dr Kobinger said that at one stage his team had “10 or a dozen” human-sized doses for research, which could be used more sparingly in animal experiments.

“Now there’s nothing left,” he added.

A Spanish missionary priest who contracted Ebola while working in West Africa and later died in Madrid had been treated with one of only three doses available in Europe at the time, said Dr Kobinger.

Subsequently, the remaining two doses appear to have been given to William Pooley, 29, from Eyke in Suffolk, the only Briton known to have been infected so far.

Mr Pooley, who caught the disease in Sierra Leone and was flown to the UK last weekend, is said to be in a stable condition at London’s Royal Free Hospital.

“The two doses used in the UK were the ones not given to the Spanish priest, that’s my understanding,” said Dr Kobinger.

However, he suggested there may have been other factors involved in the death of the priest besides the fact that he received only one dose of ZMapp.

Miguel Pajares was 75 years old, and it is unclear how advanced the disease was when he was treated.

“We know there is a point of no return where there is too much damage to the internal organs to go back,” said Dr Kobinger.

Mr Pooley’s case came to light at least two weeks after doctors attempted to save the priest.

A spokeswoman for the Royal Free Hospital said no further information about Mr Pooley’s condition or treatment had been issued since the last update on August 26.

She was unable to say how many doses of ZMapp Mr Pooley had received.

In its earlier statement, the hospital described Mr Pooley as being in “good spirits”, sitting up and talking to nurses and doctors.

It added: “After careful consideration William decided that he would like to take the experimental drug ZMapp and he took the first dose of the drug on Monday (August 25). Further doses are expected to be given to William in due course.”