Opinion

The Great Debate

Here’s the current status of new drugs to fight Ebola virus and what works best now

By Celine Gounder
September 2, 2014

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Experts will be meeting this week at the World Health Organization (WHO) to discuss the role of new drugs and vaccines to help control the Ebola epidemic in West Africa. Last month, the WHO said that it is ethical to provide experimental drugs and vaccines for Ebola, but that there’s also a “moral duty” to conduct clinical trials of these experimental drugs and vaccines to determine whether they’re safe and effective. At the same time, a new study released last week shows that the Ebola virus is mutating rapidly, which could make it more transmissible or reduce the effectiveness of drugs and vaccines in the pipeline.

ZMapp is the drug that’s gotten the most attention so far. It’s a combination of three antibodies, proteins that bind and neutralize the Ebola virus. ZMapp has been administered to seven Ebola patients, and the manufacturer says its supplies have been exhausted. It is too early to know whether Will Pooley—the British nurse who contracted Ebola while caring for patients in Sierra Leone—will survive the disease. Two of the other six ZMapp recipients have died. Those who survived may have done so because they received good supportive treatment, because they were younger and didn’t have other medical problems, or by random chance (which is more likely to happen when you’re dealing with such small numbers). While ZMapp cured 18 primates infected with Ebola virus, there’s still much we don’t know. ZMapp still hasn’t yet been studied in humans.

Other candidate treatments for Ebola include TKM-Ebola, AVI-7537, favipiravir, selective estrogen receptor modulators like clomiphene and toremifene, BCX-4430 and ST-383. In July, the Food and Drug Administration (FDA) put on hold a small trial of TKM-Ebola in healthy volunteers because the drug caused an inflammatory, flu-like response at higher doses—inflammation is also how Ebola causes disease and kills. TKM-Ebola works by shutting down the Ebola virus’ genes through a new technology called RNA interference. The FDA has since modified that hold to allow patients sick with Ebola to receive TKM-Ebola. Early human studies of AVI-7537 were stopped due to budget cuts at the U. S. Department of Defense, which was funding the trials. Favipiravir is used to treat influenza, and selective estrogen receptor modulators have been used to treat female infertility and breast cancer, so we know they are safe to use in humans. And while they show promise as Ebola drugs, they haven’t yet been studied in Ebola patients. BCX-4430 and ST-383 have yet to be studied in humans.

Vaccines to prevent Ebola are also being developed. Ebola vaccines were first tested in humans beginning in 2003. Human safety studies of an experimental Ebola vaccine developed by the National Institutes of Health (NIH) and GlaxoSmithKline will launch this week. If the vaccine appears safe, GSK plans to donate up to 10,000 doses of the vaccine to protect those at highest risk. NIH is also working with Crucell, Profectus Biosciences, Immunovaccine and researchers at Thomas Jefferson University to develop other candidate vaccines for Ebola. Human trials of the Crucell vaccine are planned for late 2015 or early 2016. Another experimental Ebola vaccine, VSV-EBOV, has been developed by the Public Health Agency of Canada and is licensed to NewLink Genetics.  Studies of VSV-EBOV among healthy human volunteers will start in October at the Walter Reed Army Institute for Research. In addition, the Canadian government is donating up to a thousand doses of VSV-EBOV to the WHO, and NewLink Genetics is trying to ramp up production of its vaccine over the coming months. Researchers have estimated that thousands, if not tens of thousands, of doses of a new Ebola drug or vaccine would be needed to help those in need.

It’s important to study and roll out new Ebola drugs and vaccines, but not at the expense of measures that we know work. We know that supportive care — to maintain adequate blood pressure, replenish lost electrolytes and treat complications — can reduce mortality from Ebola, but access to such care remains limited in West Africa. And while some of the new drugs may prove effective for treating Ebola patients, it’s unclear whether they will prevent spread of the virus from person-to-person. An epidemic can’t be contained if transmission isn’t blocked. According to Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, “we know the best way to prevent the spread of Ebola infection is through public health measures, including good infection control practices, isolation, contact tracing, quarantine, and provision of personal protective equipment.” He added, “However, a vaccine will ultimately be an be an important tool in the prevention effort. The launch of Phase 1 Ebola vaccine studies is the first step in a long process.”

In the meantime, priority must be given to identifying cases so that they may be given supportive care and isolated to prevent further spread, and to trace and test those who may have been in contact with Ebola victims. Healthcare workers need adequate supplies of personal protective equipment, and need to know how to use it to avoid being infected themselves. But it will be difficult to accomplish these goals, or to make use of new drugs and vaccines, without significant investment to strengthen health systems in the affected countries, above and beyond WHO’s US$489 million plan released last week. Meanwhile, many others are dying from malnutrition due to food scarcity, infections like malaria and typhoid, complications of childbirth and other conditions that overwhelmed, crumbling health systems are not treating.

New technologies are appealing, but they aren’t cure-alls, especially in poor, dysfunctional health systems. To illustrate this, I’ll draw from our experience with tuberculosis, which kills an estimated 1.3 million people per year globally. The most common test for tuberculosis dates back to the 1800s. Up until recently, it took up to two months to make a diagnosis of TB, allowing patients to get sicker and even die. But then scientists developed a new test, the GeneXpert, which could diagnose TB in less than two hours. Many infectious diseases and public health experts were convinced that using the GeneXpert would lead to more rapid treatment of patients, thereby saving lives. Some said that we had an ethical obligation to offer it to everyone because it was clearly so much better. In 2011, the South African Department of Health embarked on a real-life experiment of the GeneXpert. They found that using the new test made no impact on mortality. It’s not that the GeneXpert didn’t work, it’s that the test is only one small part of the process.

Diseases of the poor receive too little attention from medical researchers and pharmaceutical companies. We should be investing more to develop drugs and vaccines to combat diseases like Ebola. But we also can’t afford to wait. It’s urgent that we invest in strengthening health systems to make better use of existing tools, and eventually, new drugs and vaccines.

PHOTO: Residents of West Point celebrate the lifting of a quarantine by the Liberian government, in Monrovia, August 30, 2014. REUTERS/2Tango

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