TORONTO – Canadian research is at the heart of an experimental Ebola therapy recently given to two American aid workers infected while caring for patients in Liberia.
The unlicenced drug, called ZMapp, is made of three monoclonal antibodies, disease fighting proteins that target a specific part of an invading pathogen, in this case the Ebola Zaire virus. That is the specific strain of Ebola responsible for this outbreak.
Two of the monoclonal antibodies are the product of years of research done at the Public Health Agency of Canada’s National Microbiology Laboratory in Winnipeg, the agency confirmed in an email late Monday.
The third was developed at the U.S. Army Medical Research Institute of Infectious Diseases, known as USAMRIID.
“Canada is a world leader in research and we are proud of the advances made at the NML (National Microbiology Laboratory) in this area,” a spokesperson for the agency said via email Monday night.
The former head of the Winnipeg-based laboratory said he was delighted to hear that the Canadian-designed monoclonal antibodies had been used in this way.
“This is really gratifying to see the work come to fruition,” said Dr. Frank Plummer, who stepped down as the lab’s scientific director at the end of March.
“It’s a big achievement after years and years of very hard work.”
The Canadian research was done under the leadership of Dr. Gary Kobinger who heads the special pathogens research program at the national laboratory. His team had developed a cocktail of three monoclonal antibodies called ZMAb, the rights to which were recently acquired by LeafBio of San Diego, Calif.
LeafBio is collaborating with Mapp Biopharmaceutical, also of San Diego, which is the maker of ZMapp. That is the product given last week to Dr. Kent Brantly, who works with the relief organization Samaritan’s Purse, and Nancy Writebol, an American missionary who works with the organization Service in Mission or SIM.
The two were infected while working at an Ebola treatment centre in Liberia. Brantly was transferred to the United States last weekend, where he was admitted to a special isolation treatment unit at Emory University Hospital in Atlanta. Writebol is also being brought back to the United States; she is to arrive at Emory on Tuesday.
Neither ZMapp nor the individual monoclonal antibodies it contains have been tested in humans, though small studies in non-human primates look very promising. It has been reported that Brantly and Writebol were warned the drug had only been tested in animals but that they were willing to try the treatment anyway.
A joint statement from Mapp Biopharmaceutical and LeafBio said ZMapp is an optimized monoclonal cocktail, incorporating the best of the Canadian and U.S.-made antibodies.
The drug is generated in tobacco plants that have been genetically engineered to produce the monoclonal antibodies. That work is done by Kentucky BioProcessing of Owensboro, KY., a subsidiary of tobacco giant Reynolds American.
A spokesman for Reynolds said within the last week Kentucky BioProcessing was asked by Emory University Hospital and Samaritan’s Purse to provide a limited amount of ZMapp to be used to treat Brantly and Writebol. David Howard said the makers were given an IND — investigational new drug — designation by the U.S. Food and Drug Administration.
He said the drug’s makers hope to begin a Phase I clinical trial later this year. That type of preliminary trial involves giving a therapy to healthy volunteers to see if it is safe for people to take, and to determine an appropriate dose. These studies are not large enough to provide proof of whether a drug works.
The Canadian lab is one of the leading research facilities globally for countermeasures for Ebola and Marburg, a related virus which also causes severe and often fatal infections.
An experimental Ebola vaccine made at the Winnipeg lab under Kobinger’s predecessor, Heinz Feldmann — now head of the virology laboratory at the U.S. National Institute of Allergy and Infectious Diseases’ Rocky Mountain Laboratories in Hamilton, Mont. — is considered the best candidate vaccine for Ebola.
Unlike other experimental Ebola vaccines, the one designed at Winnipeg appears to work if given shortly after exposure to the virus, at least in animal testing. If it can be pushed through the developmental pipeline, it could be the option of choice for researchers who risk getting infected when working on Ebola in laboratories and health-care workers who can become exposed during outbreaks.
The Winnipeg lab and a number of other facilities have been working for years to produce Ebola and Marburg interventions. But lack of funding and regulatory hurdles had prevented these experimental tools from being used in outbreaks up until now.
Still, this emergency use is unlikely to change the course of the current outbreak, which continues to infect people in Guinea, Sierra Leone and Liberia and now may be moving into Nigeria. That country reported several suspect and probable cases Monday, at least two of whom are health-care workers who treated an infected man who recently travelled by plane to Nigeria from Liberia.
While there are a number of experimental therapies in development, there may be only small quantities of each available. Research laboratories and small biotech companies typically would make only what they need for research purposes. Ramping up production of a drug or a vaccine only happens when it has been licenced and the manufacturer is ready to take it to market.
The World Health Organization says that as of Aug. 1 there have been at least 1,603 cases of Ebola in this outbreak and at least 887 deaths.