by Internet Medical Society
As the lethal Ebola virus moves with unprecedented speed through West Africa, it remains a disease without a drug.
No cure or vaccine exists for Ebola, which has claimed at least 887 lives in the biggest outbreak in its history. Scientists have made significant progress in understanding the disease. But pharmaceutical companies see little incentive to invest time and money in a rare disease that afflicts relatively few people in impoverished countries.
The few drugs in the works are unapproved and years from clearing the regulatory hurdles needed to make it to market, so there is little hope of fast, widespread relief for the 1,600 people now infected.
"There's no business model for this, unfortunately," said Dr. Charles Chiu, an associate professor of laboratory medicine and infectious diseases at UCSF. "We're talking about a viral disease that really disproportionately affects the poorest segment of the population in developing countries. As a result, without incentives, we're very unlikely to see a vaccine in the near future."
Still, health officials say this outbreak could catalyze drugmakers to speed up the development process - or, in a more controversial move, lead small groups of patients to receive risky, untested treatments.
Two infected American aid workers recently took, with seeming success, a drug that had only been tested in animals. And the National Institutes of Health says an experimental vaccine will undergo an early clinical trial in humans as early as this fall.
Mass-producing a treatment, however, is challenging. A clinical trial of an Ebola drug was recently put on hold because federal regulators had safety concerns. Vaxart in South San Francisco stopped testing a vaccine two years ago because it was too expensive to pursue alone, and the company could not attract outside funding, said CEO Dr. Wouter Latour.
"I don't think there was a lot of interest back then in pursuing the Ebola vaccine as a commercial opportunity," he said.
Ebola, which had its first documented outbreak in 1976, primarily occurs in Central and West Africa. The disease first manifests with fever, intense weakness, muscle pain, headache and a sore throat; then vomiting, diarrhea, impaired kidney and liver function, and sometimes internal and external bleeding.
Lacking medicine, doctors can only replace lost blood, provide oxygen and treat other infections that develop. The current outbreak's death rate is about 55 percent, but in the past the virus has killed up to 90 percent of victims.
Humans become infected with, and spread, Ebola when they come into close contact with the blood and other bodily fluids of infected people or animals. Fruit bats are considered the likeliest carriers in nature. Burial practices in Africa, in which mourners wash and touch the dead, are also believed to play a role in transmission.
Scientists have made strides in understanding how to potentially prevent or stop Ebola. But drugmakers are hard-pressed to justify time and money on a treatment. As historic as the infection rate is, 1,600 cases is a fraction of the worldwide cases of malaria or dengue, which occur in the tens or hundreds of millions annually. And because Ebola outbreaks are sporadic, the need for a cure would be inconsistent and, some years, nonexistent.
The lack of large, constant demand means a poor return on investment for pharmaceutical companies, which on average spend a decade and $1 billion on every drug that reaches consumers.
The math did not add up for Vaxart.
Rodents given an experimental Ebola vaccine showed signs of developing the correct immune response. But to continue, Vaxart would have had to invest in labs that met the highest safety standards for handling dangerous pathogens. The United States has just six such labs.
"That's an enormous barrier for almost any company, certainly a company of our size," Latour said. Privately held Vaxart has 20 employees.
Vaxart sought government funding to support the research. Finding none, it threw its energy into pill-form vaccines for seasonal and bird flu.
Government funding will almost certainly play a large role in any Ebola drug brought to market - although not from countries where the virus is rampant. Guinea, Liberia, Sierra Leone and Nigeria are among the world's poorest nations.
"There are very promising vaccine candidates. There are also promising drug candidates," UCSF's Chiu said. "This particular outbreak might really provide resources to develop these and bring them to market and make them available."
Boosted by a $140 million contract with the U.S. Department of Defense, Tekmira Pharmaceuticals in Vancouver, British Columbia, was testing an Ebola treatment in a small group of healthy people. But the U.S. Food and Drug Administration put a hold on the trial last month out of safety concerns, causing shares to drop.
Another example is the drug given to two American aid workers who were exposed in Liberia, the second of whom arrived in Atlanta for treatment Tuesday. A humanitarian organization acquired it after learning about it from a National Institutes of Health scientist, the agency said.
Developed by privately held Mapp Biopharmaceutical in San Diego, and partially funded by federal agencies, the intravenous therapy had previously only been tested in monkeys. It is a "cocktail" of monoclonal antibodies that are designed to bind to and inactivate the virus, as well as trigger the immune system to kill infected cells.
While both Americans are said to be recovering, "it's impossible to know if patients get better on their own ... or if the cocktail of antibodies eliminated the virus," said Col.Daniel Wattendorf of the Defense Advanced Research Projects Agency, which provided funding to help develop the drug. "It's hopeful they did and very, very promising, but I don't want to speculate too early that we know for sure it worked."
In a health emergency such as this one, an experimental drug may be the best choice in some situations, Chiu said. But that approach can also have a fatal backlash.
"What happens if you give a drug to a patient with a very advanced disease ... and they die of it?" he said. "Then people will potentially blame the drug for killing the patient."