Judging An Ebola Drug In The Middle Of A Crisis
Thursday, August 21, 2014
In most cases, Ebola is a death sentence. But most of the infected patients who've taken a San Diego company's experimental drug have lived. Does that mean it works?
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Contracting the Ebola virus is a death sentence in most cases.
West Africa's current outbreak is the deadliest on record and some infected patients have been willing to try anything, including taking ZMapp — an experimental drug made by a small San Diego company that's never been tested in humans.
Not everyone treated with ZMapp has lived. But so far, five of the six patients who received the drug have survived. Although a Spanish priest given ZMapp died, three West African health workers reportedly are improving. Two American health workers, Dr. Kent Brantly and Nancy Writebol, have recovered so well that they've been discharged from the hospital.
So, does that mean ZMapp works?
"Six patients just doesn't give you enough statistical power to make a determination as to whether the drug is working," said Donald Forthal, chief of infectious diseases at the UC Irvine School of Medicine.
Forthal wonders if these patients pulled through for other reasons. Unlike most Ebola victims, they're often getting the best basic care Western medicine has to offer.
"When there's different levels of care, the outcomes may differ just on that basis," Forthal said, "rather than on the basis of the drug."
To truly know if ZMapp works, researchers would need to carefully compare large numbers of people who take it with large numbers of people who don't.
Setting up rigorous, double-blind, placebo-controlled trials in the midst of an outbreak wouldn't be easy. But Forthal says an outbreak might be the only chance to study experimental Ebola drugs.
"Clinical trials can be done there. And they really have to be done there. There won't be opportunities to do them anywhere else," he said.
Other Ebola experts see the results of ZMapp's unexpected rollout in a more promising light.
"It certainly didn't hurt them, in fact they started recovering," said Erica Ollmann Saphire, a professor at the Scripps Research Institute. "It either did nothing or it was helpful. My hunch is that it was helpful."
For the past 10 years, Saphire has been looking at Ebola under the microscope, working to pin down antibodies best suited for combating the virus, antibodies that end up in drugs like ZMapp.
Human trials haven't confirmed ZMapp's safety yet — preliminary studies are scheduled for 2015 — but Saphire is confident in ZMapp's safety and says she'd take it herself, just like those two American health workers, Nancy Writebol and Dr. Kent Brantly.
But is she equally confident the drug works?
"We didn't take Dr. Brantly and Mrs. Writebol and their identical twins, and treat one and not the twin," Saphire said. "That would be the data I would need to say confidently it works in humans."
Saphire admits we can't yet say ZMapp saved the handful of people who took it and lived. At the same time, she says the Spanish priest who took ZMapp and died doesn't prove the drug is a dud.
"He was elderly. And I think that he was infected quite some time before he was treated," she said.
Studies in primates suggest ZMapp can improve chances of survival greatly, as long as the drug is administered within two days of infection. By the time humans start displaying Ebola's worst symptoms it might be too late for ZMapp to do any good.
"The disease is a devastating disease," said Michael Kalichman, director of the Research Ethics Program at UC San Diego.
Last week, the World Health Organization determined that the use of experimental drugs in this outbreak is ethical, as long as health workers meet a "moral obligation to collect and share all data generated."
Kalichman says in a situation like this, science takes a backseat to compassion.
"A number of people said, 'Look, we have a treatment that might work. We don't have anything else that does work. Why not try?' It wasn't designed first as a research study. We get what we can from it, and that's the best, most ethical thing to do," he said.
Mapp Biopharmaceutical, the San Diego company behind ZMapp, only has nine employees. They declined to comment for this story but in a statement on their website say they're working to make more ZMapp.
The drug is grown in tobacco leaves, a process taking months. But experts say the current outbreak is poised to drag on for months. If it's still ongoing by the time more ZMapp has been produced, more of the drug could be sent to the front lines, even though researchers still aren't sure it works, or is even safe, in the long-term.
As for the six test runs of ZMapp conducted so far, what have we learned?
"Get back to me in six months and I'll be able to answer that question," Kalichman said.
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