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Experimental drug fights Ebola’s cousin Marburg; Up to 30K eligible for Ebola drugs

By Anette Breindl and Nuala Moran, Staff Writers

Scientists have reported that Tekmira Pharmaceuticals Corp.’s experimental drug candidate TKM-Marburg (NP-718m–LNP) was able to prevent monkeys from becoming seriously ill after Marburg virus infection, even when treatment was not started until the animals showed signs of viremia.

They published their work in the Aug. 21, 2014, issue of Science Translational Medicine.

Senior author Thomas Geisbert, who is at the University of Texas Medical Branch, told reporters at a press conference announcing the findings that the late treatment onset demonstrated the “real world utility” of the technology, giving hope that effective treatments for Marburg, as well as its currently attention-hogging cousin Ebola, could be developed.

The technological approach used in the present studies, siRNA delivered in a lipid nanoparticle, also has been used to protect Macaque monkeys from death due to Ebola infection, although in the earlier Ebola study the drug was given soon after exposure.

Therapeutics for hemorrhagic viruses are developed under the FDA’s two animal rule; that is, for FDA approval they have to be effective in two animal species and safe in humans.

With the new paper, data in two animals – guinea pigs and monkeys – exists for the Marburg drug.

Geisbert said it would take “less than a year, probably, for a clinical trial, but it really depends – we don’t have the funding… today for a clinical trial for the Marburg product.”

The experimental Ebola drug, on the other hand, had satisfied the two-animal rule in 2010 – but at the time, funding for human trials was not forthcoming, though a clinical trial is now being funded through the Department of Defense.

In their experiments, Geisbert and his colleagues at the University of Texas and Tekmira used siRNAs delivered in lipid nanoparticles to block translation of Marburg virus mRNA.

The sequences used in the study were targeted to conserved sequences of Marburg virus and would be expected to be effective against all major strains. MARV-Angola, the strain used to test in the work now reported in Science Translational Medicine is the deadliest known, with fatality rates of about 90 percent in the 2005 outbreak that was due to this particular strain.

Geisbert and his team infected monkeys with high levels of MARV-Angola and began treatment with TKM-Marburg between 30 minutes and three days after infection.

Even when treatment was not started until the third day, TKM-Marburg completely protected the animals. None of the treated animals died, and only a few of them even developed a fever or rash.

The experimental setup does not wholly mirror the course an infection with Marburg virus would take in the real world, due to both ethical and financial imperatives to minimize the number of primates used. Geisbert estimated that the third day after experimental infection would be equivalent to the sixth or seventh day after a naturally occurring infection.

But the key point, he added, was that treatment was not initiated until there were detectable signs that an infection had occurred. The team currently is testing how long treatment can be delayed and still be effective. 

Researchers: Up to 30K eligible for Ebola drugs in ‘conservative’ estimate

LONDON – The scale of the current outbreak of Ebola presents a change in the development landscape for therapeutics, with a far greater demand for drugs than is realized, according to new epidemiological research.

While the World Health Organization (WHO) has acknowledged the existing stocks of experimental drugs that could potentially be used to treat Ebola are insufficient to meet the size of the outbreak, the question of by how much supplies need to be boosted was left hanging.

Now, scientists at Oxford University, who have attempted to estimate which kind and what volume of treatments are needed, said the demand is likely to be higher than many people realize. “Our analysis suggests that even under a conservative scenario, up to 30,000 people would so far have required treatment or prophylactics in the current outbreak,” said epidemiologist Oliver Brady, writing in the Aug. 21, 2014, issue of Nature.

Brady and colleagues in Oxford University’s Spatial Ecology and Epidemiology Group, who specialize in mapping the global distribution of infectious diseases, are seeking to forecast requirements, following the WHO decision last week that the severity of the Ebola outbreak in West Africa makes it ethical to use unregistered drugs and vaccines.

Following that recommendation, the WHO is due to bring together a group of experts to weigh the ethical criteria by which to prioritize who should receive which products. Three classes of drugs – antiviral, antibody-based and vaccines – will be considered at the meeting, which will take place before the end of the month. (See BioWorld Today, Aug. 13, 2014.)

Given that backing from the WHO, “policymakers and funders are now trying to decide which of these options to accelerate into active service. They need good estimates of how many of these drugs and vaccines to manufacture and distribute,” Brady said.

Brady and his colleagues have separated the people who need treatment into four categories: those infected with Ebola and people in close association with them such as family members; medical staff treating patients and those handling corpses; support staff such as aid workers and those providing key services and logistical support in dealing with the epidemic; and people who have travelled to the area of the outbreak in west Africa and show possible symptoms of Ebola on their return.

Based on current scientific understanding about probable levels of exposure in these groups, the researchers have calculated the total number of people who might require treatment for a given outbreak and how many will be in each category. The intention is not to provide exact numbers of doses required but rather “to scope potential demand” in different scenarios.