Ebola death toll passes 1,900 as WHO mulls new therapies

As the Ebola outbreak shows no signs of abating, the World Health Organization (WHO) has convened a meeting to establish the best way to use the vaccines and drugs being developed to fight the deadly virus.

At last count the number of people who have died from Ebola – mainly in West African countries Guinea, Liberia and Sierra Leone – was approaching 3,500 and the WHO fears there could be 20,000 cases or more before the outbreak is contained.

The agency has been scouring the globe to identify drugs and vaccines that are in development for Ebola now that the limited supplies of the experimental ZMapp treatment from Mapp Biopharmaceutical – used to treat a handful of patients – have been exhausted.

One of the most accessible therapies under discussion is to use the antibody-laden blood of the thousands of Ebola survivors as a form of passive immunity for other infected individuals in the hope that it may tip the balance in favour of recovery. The WHO has suggested it may be able to start screening, collecting and processing survivors’ blood later this year.

The logistics of collecting this so-called ‘convalescent plasma’ from the patients, the variability of antibody levels between patients and the risks of co-infection with diseases like HIV and malaria could however limit this approach, according to the agency.

Donated blood has reportedly been used in a handful of cases in the latest outbreak, including for American doctor Kent Brantly, who also received ZMapp and survived the infection.

A drug- or vaccine-based approach would be preferable in the long-term, as it would be less variable, but the WHO wants a systematic review of the available options to help counter “unrealistic expectations … in an emotional climate of intense fear.”

“The public needs to understand that these medical products are under investigation. They have not yet been tested in humans and are not approved by regulatory authorities,” it said in a report to be discussed at the ongoing meeting.

Last month the WHO said that it was medically ethical to allow untested drugs to be made available to Ebola patients as this is “the largest, most severe and most complex outbreak of Ebola virus disease in history.”

Aside from convalescent plasma, the blood of survivors could also be used to isolate and purify the antibodies from the blood of survivors or immunised animals to create hyperimmune globulin stocks against Ebola, but this will take months to achieve. Work is starting in cattle and horses but it will be the middle of next year before stocks are available for use in humans.

The WHO is also discussing Tekmira’s gene-silencing therapy TKM-Ebola, which has been authorised for emergency use by the US Food and Drug Administration (FDA) despite side effects such as chest tightness and increased heart rate in early trials. A limited number of doses are available at the moment with an estimated 900 potentially ready for use early next year.

Other candidates on the table include Sarepta’s AVI 7537 – with 25 courses available right now and the potential for another 100 more in early 2015 – Toyama’s favipavir which is already approved for serious influenza cases in Japan and could have as many as 10,000 courses available – and BioCryst’s BCX4430, which is in the very early stages of development. The latter needs animal data “before it can be considered,” according to the WHO.

One of the biggest questions facing the WHO panel will be the possible role – if any – of interferon-based drugs, which are commercially available and so could be deployed quickly. However, decisions regarding which type to use, the timing and dosage regimen in Ebola “need careful consideration,” it says.

Vaccine hope

The ideal solution to the Ebola problem would of course be an effective vaccine that could be used to curb the spread of infection and protect emergency and healthcare workers, although there are fewer candidates to choose from at the moment.

The vaccine based on Chimpanzee adenovirus serotype 3 (ChAd3) developed by GlaxoSmithKline and the US National Institutes of Health (NIH) seems to be near-term option in terms of supply with up 15,000 doses potentially available by the end of the year. Meanwhile around 800 doses of a Canadian recombinant vesicular stomatitis virus (VSV) vaccine are already available and is due to start trials shortly.

Meanwhile, Johnson & Johnson has just revealed that it is fast-tracking its own vaccine candidate – developed by Dutch subsidiary Crucell in collaboration with Danish biotechnology company Bavarian Nordic – which has already been tested in macaque monkeys. Human trials are expected to start within weeks, but at the moment there is no indication how quickly production could be ramped up.

The WHO said it will try to establish the best way to deploy and evaluate the various treatment and vaccination options on the table along with almost 200 international experts – including policy-makers from Ebola affected countries, ethicists, clinicians, researchers, regulators and patient representatives.

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