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Ebola: still no cure

Brigitte OsterathDecember 11, 2014

In August, the World Health Organization said treating Ebola patients with unapproved drugs was ethical. It was hoped it would speed up research. Months later, an approved Ebola drug remains far off.

Symbolbild Ebola
Image: Cellou Binani/AFP/Getty Images

Developing a new drug takes about ten years. But recent events have shown it may happen faster - if international pressure is big enough.

Ebola drug development did not have to start from scratch when the outbreak in West Africa began. Public research institutions had been developing candidate drugs in the lab, and tested them in animals experiments.

All that was needed were clinical trials in humans.

But human trials take time.

About four months after the World Health Organization said it was ethical to use untested - or unapproved - drugs on Ebola patients, we're still without a licensed drug.

Researchers are working on several Ebola drug "candidates" - but still, no known drug works for sure in humans.

Promising but depleted

ZMapp was the first Ebola drug candidate to make media headlines when two US citizens were given it and recovered.

It was unclear, however, whether ZMapp was directly responsible for their recovery.

Shortly after the case of the two US citizens, a Liberian doctor and a Spanish priest died despite taking the drug.

ZMapp is a mixture of three antibodies. They block or neutralize the virus by binding to the covering or envelope of the virus - its outer surface.

Animal experiments with Ebola-infected monkeys had been successful - all treated animals survived.

But up to now, no formal safety studies exist. And the WHO says it is still uncertain whether ZMapp works in humans.

In addition, the supplies of ZMapp are limited due to the drug's complicated manufacturing process using genetically modified plants.

Tobacco plants Photo: Sean Gallup/Getty Images
Genetically modified tobacco plants are used for a candidate Ebola drugImage: Gallup/Getty Images

In mid August, US producer Mapp Biopharmaceuticals said their supplies were exhausted.

The company says it is working with the US government to quickly scale up production.

Limited supplies a general problem

A statement from Doctors Without Borders says "We cannot exclude a scenario where a drug or vaccine is found safe and effective, but has to be rationed because available quantities are limited."

This is not only true of ZMapp.

So-called RNA interference therapeutics are also difficult to produce.

These drugs consist of RNA, a complex biomolecule that stops a virus from replicating.

One such promising candidate is TKM-Ebola by the Canadian drug company Tekmira.

In guinea pigs and monkeys, the drug cured Ebola.

A clinical trial evaluating the safety in humans, though, found some side effects like chest tightness and increased heart rate.

As a result, the FDA placed this clinical trial on hold.

Against flu - and Ebola, too?

Flu and Ebola have one thing in common - both are caused by viruses.

Antivirals stop viruses - such as the flu virus - from replicating inside the body.

There is a hope such drugs, taken in a higher dose, will tackle the Ebola virus, too.

Clinical trials with two antivirals will start shortly. These drugs are Favipivavir, developed in Japan, and Brincidofovir, developed in the US.

The French Institute of Health and Medical Research and the University of Oxford will test these drugs in Ebola treatment centers hosted by Doctors Without Borders in West Africa.

"Consultations on the design of these studies are almost in their final stretch," says Philipp Frisch of Doctors Without Borders.

The trials "will start as soon as possible, hopefully this month," Frisch says.

Treatment Center in Guinea Photo: CELLOU BINANI/AFP/Getty Images
Three Ebola therapies will be tested in treatment centers in GuineaImage: CELLOU BINANI/AFP/Getty Images

Choosing the best drugs for trials

Antiviral drugs have one big advantage: They consist of small chemical molecules that are quite easy to produce.

That was one of the reasons why these drugs were chosen for clinical studies, Frisch says.

Another reason is that researchers have already tested these two drugs for safety in humans.

Favipivavir is approved in Japan for treating influenza. Brincidofovir is unapproved, but a lot of safety data have been gathered.

The WHO's Scientific and Advisory Committee on Ebola Experimental Interventions, though, found in November that preclinical data regarding these drugs' effectiveness against Ebola was less than promising.

Some members of the committee said availability alone "was not a reason to study drugs with weak supporting data."

Natural weapons against Ebola

Researchers also hope to extract antibodies from the blood of animals that have come into contact with the Ebola virus.

This treatment option is considered safe, but animal-produced antibodies are currently unavailable as the purification process takes several months.

The WHO says large-scale batches are not expected before mid-2015.

Blood transfusion Photo: Gina Sanders - Fotolia.com
Clinical trials will test the potential of using blood from Ebola survivorsImage: Fotolia

Another option would be to transfuse the blood plasma from Ebola survivors to infected people as the plasma contains antibodies against the virus.

The Institute for Tropical Medicine in Antwerp will soon begin testing this method in the field at a Doctors Without Borders treatment center in Guinea.

"This method is more complicated than it sounds," says Frisch.

The survivors' blood has to be tested and purified before doctors can give it to a patient.

Against all financial principles

Whichever drug comes out ahead in clinical studies, Doctors Without Borders says it is important to start thinking about upscaling production now.

"We cannot afford to lose any time before production is ramped up," the agency writes in a statement.

Normally, a drug is fully-tested before a company starts to think about how it will scale up production.

Economically, it is the only way that makes sense.

This time, though, economics shouldn't be the priority.

There is no point in finding an effective drug if it remains unavailable to thousands of dying Ebola patients.