The speed and scale of the outbreak and its arrival in the U.S. has also prompted manufacturers that haven't focused their research on Ebola to consider nontraditional pathways to test unapproved drugs to treat the disease. Philadelphia-based Hemispherx Biopharma said this week that it hired law firm Squire Patton Boggs to “find additional pathways” to test Ampligen, its experimental anti-viral drug, and Alferon, an anti-viral approved to treat genital warts.
About 9,200 Ebola cases have been reported worldwide, according to the Centers for Disease Control and Prevention. Three have been diagnosed and treated in the U.S., and a few others have been flown to the U.S. for treatment after contracting the disease as aid workers in West Africa, the center of the outbreak.
The FDA, under its authority to expand access to an experimental treatment, can grant emergency investigational new drug applications when a treating physician requests a drug. The FDA can also utilize a regulation referred to as the Animal Rule (PDF), which allows certain products to be tested for efficacy in animals. The FDA has said that getting a drug approved under the Animal Rule means that the efficacy studies in humans could not be conducted because it would be unethical and trials would not have been feasible.
Still, the FDA's options raise both ethical and safety questions. What's the best way to develop data in an expedited review? Who gets to take the drug? If product is limited, what patients should use it first?
“This is unusual because you've got such a serious health crisis,” said James Cohen, head of the FDA practice at the law firm McDermott Will and Emory. “It's comparable to traditional vaccine development when there are potential shortages or significant shortages that can led to serious health issues or crises, or biological threats.”
A randomized clinical trial is considered the gold standard for drug development, but trials may take too long and would require some infected patients to receive a placebo rather than treatment.
The global medical community differs on how best to handle that process and medical ethicists in recent months have argued both sides in the pages of medical journals. Dr. Steven Joffe, vice chair of the medical ethics and health policy department at the University of Pennsylvania, wrote in JAMA this month that randomized clinical trials are the best way to conduct Ebola research. A group of scientists and bioethicists took the opposite stance in the Lancet.
“We accept that (randomized clinical trials) can generate strong evidence in ordinary circumstances; not, however, in the midst of the worst Ebola epidemic in history,” the authors wrote in the Lancet. “The urgent need is to establish whether new investigational drugs offer survival benefits, and thus which, if any, should be recommended by WHO to save lives. We have innovative but proven trial designs for doing exactly that. We should be using them, rather than doggedly insisting on gold standards that were developed for different settings and purposes.
But there are other questions beyond the design of the clinical trial and review process. Some experimental therapies are already in short supply, such as ZMapp, which was developed by Mapp Pharmaceutical. The drug's antibodies are taken from tobacco plants. As of Aug. 12, the company's supply of ZMapp was exhausted and remains so.
This is one reason that some analysts say Chimerix is a frontrunner. The company is in phase III clinical trial using brincidofovir to prevent cytomegalovirus in renal transplant patients. The drug has been used to treat more than 1,000 patients for safety and efficacy, has large-scale manufacturing in place and can be distributed in tablet form, said Katherine Wu, an analyst for investment bank William Blair.
“Once efficacy is demonstrated in either infected animals or humans, brincidofovir could be used in Ebola patients broadly and Chimerix could receive stockpiling orders from various governments,” Wu said in an Oct. 15 research note.
The company has said it is in discussions with the CDC to also use brincidofovir as a prophylactic treatment for patients exposed to Ebola, Wu said in an interview.
Hemispherx expects Squire Patton Boggs to help the company “educate the federal government about the availability and potential” of its drugs to treat Ebola while also communicating the same message to the overseas governments that are dealing with the outbreak, said Kevin O'Neill, the firm's deputy global managing partner for public policy, investigatory and regulatory solutions. “Other companies have gotten their products made available to address the crisis,” he said.
Follow Jaimy Lee on Twitter: @MHjlee
