U.S. government researchers are working hard to get an experimental flu drug from Japan’s Fujifilm Holdings Corp. quickly approved to treat Ebola, as the death toll rises in West Africa.
Fujifilm’s U.S. partner MediVector Inc. in Boston is in talks with the Food and Drug Administration to submit an application to use the drug in humans for Ebola, according to Department of Defense spokeswoman Amy Derrick-Frost. If successful, the treatment drug would be one of the first allowed by U.S. regulators to fight the disease in humans.
The Department of Defense has prioritized the completion of a study that tests the drug called favipiravir in Ebola-infected monkeys, Derrick-Frost said. The drug can be fast-tracked through the regulatory review process after the studies are complete, she said. Preliminary monkey data are expected in mid-September, she said.
The advantage of using favipiravir in an Ebola outbreak is that it has already been extensively tested for use as an anti-viral in human trials for influenza. The drug is now in a U.S. final-stage trial for treating influenza.
In addition, the drug is a pill, unlike the cocktail of injected antibodies administered to two Americans who got Ebola. This means it may be easier to use in rural locations with limited medical infrastructure.
On August 5, a spokeswoman for MediVector declined to comment on the possibility of human use of the drug in Ebola, and deferred questions on subject to the Department of Defense.
Fujifilm rose 5.4 percent to 3,089.5 yen in Japan trading today, the biggest gain in more than a year.
The world’s worst Ebola outbreak comes at a time when promising treatments are finally starting to emerge from the laboratory, many of which are the products of years of research funded by the U.S. military.
“There has been tremendous progress over the last five to 10 years in developing vaccines and post-exposure treatments” for Ebola, said Thomas Geisbert, a virologist and veteran Ebola researcher at the University of Texas Medical Branch at Galveston.
At least four to five different vaccines and three treatments have been shown to protect monkeys from doses of Ebola that would normally be lethal, he said. He is working to test combinations of drugs and vaccines that may have even greater effectiveness.
In addition to the Mapp Biopharmaceutical Inc. antibody cocktail drug that was used in two Americans who contracted Ebola, drugs that have helped monkeys survive Ebola include TKM-Ebola from Tekmira Pharmaceuticals Corp. in Burnaby, British Columbia. The drug protected all four monkeys who received seven doses of the treatment after being infected with high-doses of Ebola in a 2010 study led by Geisbert. Federal regulators put a safety study of the drug in healthy volunteers on clinical hold in July.
Stephanie Yao, an FDA spokeswoman, said that while the agency couldn’t comment on the development of a specific product, it considers each human study individually based on assessments of the risks and benefits involved.
“A future proposal for a study or emergency use in a different population, for example in patients with disease, might have an acceptable risk-benefit balance,” she said. “If the benefits of studying the product on an individual outweigh the risks, we may consider permitting that study to proceed.”
Favipiravir was discovered by Yousuke Furuta at the Toyama Chemical unit of Tokyo-based Fujifilm in 1998. It targets polymerase, an enzyme viruses use to replicate inside the body, to stop the viruses from spreading.
The Department of Defense in 2012 awarded a $138.5 million contract to MediVector to further develop favipiravir against multiple influenza viruses. Fujifilm retains the rights to the drug.
While human tests in influenza are far along, two studies in mice published earlier this year suggested that favipiravir could protect the animals against Ebola.
Tests of Ebola drugs in mice don’t always predict whether an Ebola drug will work in larger animals, said Geisbert. Showing effectiveness of an Ebola treatment in monkeys as well is important because the disease course in monkeys “is almost identical” to that in humans, he said.
With no commercial market for an Ebola drug, many of the companies working on Ebola treatments are small outfits that have been working with military funding, said Arthur Caplan, director of the division of medical ethics at NYU Langone Medical Center. That means supply of any experimental drugs is likely to be very limited, he said.
“The biggest ethical question is rationing -- who gets the scarce supply,” said Caplan in a telephone interview.
“We are not going to get very far unless someone helps with a big donation” to ramp up manufacturing, said Caplan. “They are little companies at the experimental phase and they simply don’t have very much supply.”
If the U.S. Food and Drug Administration gives some kind of accelerated approval for an Ebola drug, that could provide guidance for developing countries, said David Heymann, an infectious disease expert at the London School of Hygiene and Tropical Medicine, who has studied Ebola since the first outbreak in 1976. The World Health Organization will also play a crucial role because developing countries tend to follow its advice, he said. It is convening a panel of medical ethicists next week to explore use of experimental treatments for Ebola.
The defense department has been funding U.S. clinical trials of the medicine for influenza as part of its effort to boost the country’s biodefense capabilities and protect the military against flu pandemics. Approval as an Ebola treatment would give doctors one of their earliest weapons to fight the disease, which the World Health Organization estimates has killed more than 900 in West Africa.
A Mapp Biopharmaceutical experimental drug called ZMapp that was given to two Ebola patients recently hadn’t been previously tested in humans. The Biomedical Advanced Research and Development Authority is currently exploring whether it’s possible to ramp up development of Mapp’s drug and if so, how it could be done, the federal authority’s director, Robin Robinson, said in an e-mail.
BioCryst Pharmaceuticals Inc. has an antiviral drug that showed in a study this year it could treat monkeys infected with Marburg virus, a relative of Ebola. On an earnings conference call on August 5, a company executive said that “the next step” in Ebola would be to conduct a similar study of the drug in monkeys infected with that virus.
Fujifilm spokesman Takao Aoki declined to comment on whether the company had been asked to supply its medicine to treat Ebola patients. The FDA said the companies developing drugs have to file for the fast-track review process but declined to comment on whether it was in talks with MediVector.
Favipiravir is in the final stages of human studies in the U.S. as a treatment for flu. A Phase II study in the U.S. using 10 grams of the drug showed the medicine reduced flu symptoms against a placebo. The U.S. phase III study of the treatment for flu is scheduled to be completed around March 2015, the company said last month.
The U.S. Department of Defense funded the trials to improve the country’s response capability and protect the military from flu pandemics, its BioDefense Therapeutics unit said in an October statement.
Favipiravir won Japanese approval in March for government stockpiling for pandemic flu after the mid-stage U.S. study showed the reduction in symptoms.
Fujifilm is running a trial and is in discussion with Japanese regulators to get marketing approval to sell it for seasonal influenza, Kouichi Yamada, senior operations manager of Fujifilm’s drug products division, said in an interview in July.
Ebola, first reported in what is now the Democratic Republic of Congo in 1976, can cause bleeding from the eyes, ears and nose and spreads through direct contact with body fluids such as blood and urine. The virus, which has historically killed as many as 90 percent of those who contract it, has a fatality rate of about 60 percent for the current outbreak, probably because of early treatment efforts, officials have said.
With no proven cure for Ebola, patients are normally given fluids, blood transfusions and antibiotics with the hope their immune systems can fight off Ebola’s onslaught.
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