Mapp Bio Steps onto Global Stage as Ebola “Hot Zone” Gets Hotter

Xconomy San Diego — 

The “hot zone” in West Africa that has become the worst Ebola outbreak in history is now a full-blown global health crisis—and it is expected to continue into 2015.

That is the consensus of three Ebola experts who, speaking at a public forum in San Diego, joined a growing number of world health officials in warning that the thousands of known and suspected Ebola cases may be just the beginning in a protracted battle to bring the letal viral contagion under control.

The forum, held in a lobby of The Scripps Research Institute (TSRI) Wednesday, included a rare public appearance by Kevin Whaley, CEO of Mapp Biopharmaceutical, the tiny San Diego biotech that developed ZMapp, the experimental anti-viral drug given to American missionaries Kent Brantly and Nancy Writebol, as well as a Spanish priest and three African healthcare workers—who were all stricken with Ebola. One of the African healthcare workers, Dr. Abraham Borbo of Liberia, and the Rev. Miguel Pajares of Madrid, nevertheless succumbed to the disease.

Whaley, who has avoided the celebratory publicity surrounding ZMapp, said he and co-founder Larry Zeitlin “both came out of the school of public health at Johns Hopkins,” and founded Mapp Bio in 2003 to serve the “unmet needs in global health.” The company has only nine employees and is focused primarily on the health needs of mothers and children in “under-funded and under-appreciated” places like West Africa.

Kevin Whaley

Kevin Whaley

The unassuming Whaley declined to say much about his feelings after Brantly and Writebol walked out of the Emory University Hospital in Atlanta, where they were hospitalized after receiving the first doses of ZMapp ever administered to humans. While the experience was “certainly very satisfying,” Whaley said ZMapp was not given in a way that could yield any scientifically validated data or conclusions. “Any skeptical scientist would have to say there is no way to know” whether the drug contributed to the four survivors’ recovery, he said.

With all available samples of ZMapp now exhausted, Whaley said Mapp Bio is looking for major help from the federal government to make more.

Meanwhile, the World Health Organization said Thursday the Ebola outbreak could infect more than 20,000 people before it is over. Tom Frieden, director of the Centers for Disease Control and Prevention (CDC), told CNN Wednesday that the situation in Liberia is worse than he expected. Because Ebola symptoms can take weeks to develop, Frieden said the risk of exporting Ebola to another country increases every day the outbreak goes on.

Health authorities have counted 1,552 deaths in at least 3,069 suspected or confirmed Ebola cases since the outbreak began at the beginning of this year, according to an update posted on the CDC website Thursday. The disease has spread to four countries in West Africa: Sierra Leone, Liberia, Guinea, and Nigeria. As the crisis mounts, the U.S. and U.K. are finally moving to test a new Ebola vaccine for the first time in humans. Three early stage  trials are slated to start soon—two in the U.S., one in the U.K., Mali and the Gambia—and data are expected by the end of the year.

Whaley was one of three experts invited to talk about the lethal Ebola virus and how efforts to contain the epidemic are faltering in West Africa. Nearly 200 people attended the discussion, which often strayed into funding appeals as the experts described how reductions in federal support for biomedical research and last year’s budget sequestration have hamstrung basic biomedical R&D.

“There has been no comparable response to the Ebola outbreak that was seen with the [2011] tsunami in Japan and the [2010] earthquake in Haiti,” said Erica Ollmann Saphire, who studies the molecular basis of viral pathogenesis at TSRI.

U.S. health agencies that once awarded funding to the top 25 percent of research grant applications a few years ago are now handing out grants only to the top 7 or 8 percent, Saphire said.

Erica Ollmann Saphire, structural cell biologist, virology, pathology

Erica Ollmann Saphire

An international research consortium that Saphire leads also lost funding needed to operate a clinic in Sierra Leone that examined nearly all of the country’s patients in the first month of the Ebola outbreak. Automated cuts mandaded by the budget sequestration for the fiscal year that began last October deleted $100,000 needed to run the clinic and pay about 30 healthcare workers, said Saphire, who appealed for donations to keep the clinic going.

Meanwhile, there is no cure for Ebola, Saphire said. The virus replicates so rapidly that a patient’s immune system is literally in a race against death. In addition to advancing experimental vaccines and drug candidates, such as the cocktail of monoclonal antibodies developed by Mapp Bio, Saphire said new methods for rapidly diagnosing Ebola infections are also badly needed.

With current tools such as a cell-culture assay or a PCR-based genetic test, it can take days to determine if a patient is battling Ebola. Saphire said her lab has been trying to develop a “dip stick diagnostic”—like a pregnancy test—that uses antibodies to immediately signal the presence of the virus.

Saphire said her lab, like Mapp Bio, is completely reliant on federal funding to continue its scientific research and development. Although Whaley said Mapp Bio is “working aggressively to pull materials together,” it was clear the little company is depending on the government to accelerate ZMapp production and move toward clinical trials.

When asked how long that might take, Whaley was presumably referring to the government when he said, “They are doing everything they can, both technically and from a financial point of view.”

When asked how ordinary folks can help, Mark O’Donnell of Project Concern International (PCI), a San Diego non-governmental organization that provides humanitarian and public health assistance in Liberia and elsewhere said, “The short answer to what’s needed now is more funding.”

In Liberia, where the number of Ebola cases is doubling every 35 days, O’Donnell said food shortages and violence have left the government reeling. What was known as a health emergency in March, when PCI joined the public health effort against Ebola in Liberia, is now “a dire crisis,” he said. “People are running scared, and rightfully so. It’s fair to say that certain systems are crumbling.”

PCI provides medical supplies, training for healthcare workers, and public health awareness and education, O’Donnell said. As the epidemic has spread, there have been shortages of basic medical supplies like masks, gowns, and gloves. As a result, O’Donnell said 360 healthcare workers have contracted Ebola, and about 70 percent died.

“A doctor shouldn’t die because he doesn’t have gloves to wear,” Saphire observed. “This is a solvable problem.”

Ebola virus (image: Cynthia Goldsmith/CDC)Even so, American medical volunteers and healthcare workers in West Africa are trained to work with Ebola, which is spread by direct contact with the blood or bodily fluids of infected patients. A spot of blood that is 1 square centimeter might have as many as 1 billion viruses, Saphire said, and healthcare workers can make mistakes when they are working 15-hour days.

Nevertheless, “These are highly trained personnel who know what they’re up against,” she added. “So how did they get infected? That is a real mystery, and something we need to know.”

In contrast to previous Ebola outbreaks, which had mortality rates as high as 90 percent and were usually confined to remote villages where infections “burned out” within a few weeks or months, Saphire said the contagion along the West African coast has lasted longer and spread farther to become the worst Ebola outbreak in history.

One factor might be that this Ebola virus has a lower mortality rate. It kills about 50 percent of those infected, according to the CDC.

Other clues may lie in a study published today in the journal Science. Scientists at the Broad Institute and Harvard University, working with Sierra Leone Ministry of Health and Sanitation, found more than 300 genetic changes that make the 2014 Ebola virus genomes distinct from the viral genomes analyzed in previous Ebola outbreaks.

“One of the things we will be doing in my lab is looking at all those mutations” to see if there is something there that makes the virus replicate more easily, or makes it easier for the virus to suppress an immune response, Saphire said. Every Ebola lab in the world also has been identifying antibodies that bind to the surface of the Ebola virus, and forwarding their findings to Saphire’s lab.

With more information like this, she said it may be possible to identify new or different combinations of antibodies that work more effectively to stop Ebola. All it takes is time and money. If only there were more of both.