Two new drugs have shown remarkable promise at treating Ebola in a clinical trial, increasing survival rates for people who recently contracted the disease to between 89 and 94 percent. That’s astonishing for a virus that typically kills about half of all the people it infects.
“From now on we will no longer say that Ebola is not curable. This advance will in the future help save thousands of lives that would have had a fatal outcome in the past,” Jean-Jacques Muyembe, director general of the Democratic Republic of the Congo’s Institut National de Recherche Biomedicale, announced in a press call.
In the aftermath of the discovery, the ongoing outbreak in the Democratic Republic of the Congo is now being viewed by experts not only as a major turning point in Ebola R&D, but also in the way drugs are developed for future emerging diseases. In the past, Ebola has broken out in poor and conflict-ravaged communities that have little access to health care. That’s posed challenges when it comes to securing the investments to fund a cure, and it has made drug trials amid crises even more challenging.
That makes the success of these two drugs all the more exciting to scientists. “This is the first time that a randomized, controlled trial has shown quickly and successfully what the best drugs are in the middle of an ongoing outbreak,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health, said.
Ebola first emerged more than 40 years ago, and it sparked global fear after massive outbreaks in West Africa between 2014 and 2016 killed more than 11,300 people. Smaller outbreaks have continued, including an ongoing crisis in Congo where nearly 2,800 people have been diagnosed and more than 1,800 people have died. The World Health Organization declared it a public health emergency “of international concern” this July.
Often, in the midst of an epidemic of that scale, Fauci explains, there’s pressure to deploy drugs to the public that may have looked promising in the lab but lacked rigorous clinical trials to prove their safety and efficacy. The outcome of this trial, he contends, is evidence that even in the most challenging situations, studies can be conducted to ensure that a drug is safe.
This particular trial started in November 2018 as part of the international emergency response to the epidemic in Congo. A joint effort by several Congo and international medical organizations enrolled roughly 700 patients to try four experimental drugs. The two more promising treatments are called REGN-EB3 and mAb114, which work by intravenously infusing a combination of monoclonal antibodies into the patient’s blood. The other two drugs, remdesivir and ZMapp, will no longer be administered since they resulted in death rates up to 3 times as high as the other two drugs in patients with low viral loads.
The two Ebola drugs that have succeeded are being offered at no cost for “compassionate use” even though they’re still technically experimental. The process of actually getting a drug through regulatory agencies and into commercial availability is long and cumbersome. Up to 12 years can pass between the time a drug is patented and when it hits the marketplace. And the cost of seeing a single drug through from concept to commercial availability can reach upwards of a billion dollars.
There can be additional hurdles for drugs that treat what are often called “orphan” or “neglected” diseases, which are those that usually afflict communities in the global south that don’t have the funds or political clout to make a drug profitable. Without incentive or investment, drug candidates can get lost in what’s often called the pharmaceutical “valley of death.”
“There is no natural market or demand for a product until an outbreak actually occurs and because outbreaks are sporadic and unpredictable, the size and scope of that market is unclear,” Jamie Bay Nishi, director of the Global Health Technologies Coalition, which advocates for the research and development of neglected diseases, in an email. “Private sector companies have limited incentive to invest proactively, leaving us without tools needed to confront these crises.”
Daniel Bausch, virologist and director of the UK Public Health Rapid Support Team, said, “Ebola is really the canary in the coal mine of populations where the right to health has not been upheld.” His team contributed to some of the training and preparation for the Congo drug trial.
Bausch has studied and worked in Ebola response since the mid-1990s. Like Fauci, he believes that the recent success in finding a cure represents a marked shift in the way the world might respond to infectious disease threats in the future. It’s a “different world” he says, in comparison to “this idea that we had really ingrained prior to the west Africa [Ebola outbreak] that development of a drug had to be a decades-long thing and multi-millions of dollars.” Ebola has shown that the process can be sped up.
Still, Bausch cautions that there are some factors that make Ebola an exceptional case. For one, it’s a high-profile disease. “Everyone was ready to speed up and contribute and do things with Ebola that they don’t routinely do because Ebola is such a dire situation,” he says. “There are a lot of bad diseases in the world, but there’s not many that provoke the same sort of response and kind of an all-hands-on-deck approach to things.”
Another interesting fact about Ebola: years prior to the outbreaks in Africa, the US Department of Defense had already penned contracts worth hundreds of millions of dollars with various pharmaceutical companies to explore drug therapies for Ebola. That’s in part because the disease had been classified as a bioterrorism threat by the Centers for Disease Control and Prevention since 2004. “One of the reasons that we had some of these compounds ready for study for Ebola was because there was a concern and has been a concern of Ebola as a bioweapon,” Bausch says. That’s not the case for many other understudied diseases with no vaccine or medicines, like the Nipah virus.
Nonetheless, thanks to the recent drug trial in Congo, Bausch adds: “I think we have to be very optimistic and very proud that we can really do the sound science and get answers in the most difficult settings.” And that may extend to outbreaks of other diseases in the future.
According to Nishi, government investment is absolutely essential to advancing products for any neglected and emerging diseases through development. In the case of Ebola, US funding and political commitment were key to the recent achievement, as was the collaboration of other states and humanitarian organizations. But this can also create more questions for the future of Ebola treatments.
“As we move forward, who pays and will drug companies have a motivation to push this through all the way to a commercially available, FDA-approved product? Assuming so, then who pays for it the next time around?” Bausch said. “We haven’t gotten that far yet. Those questions will emerge now because we take one step at a time.”