Unproven Ebola Drugs Are Ethical to Use in Outbreak: WHO

Developers of unproven Ebola drugs received backing from medical ethicists to deploy the therapies against the worst outbreak of the deadly disease on record.

The decision, by a panel of outside advisers to the World Health Organization, gives stricken West African nations more confidence to request drugs and may yield valuable information on whether, and how, the medicines work. Finding doses poses an immediate challenge after one drugmaker, Mapp Biopharmaceutical Inc., said yesterday it’s already exhausted its supply.

There are no approved drugs or vaccines against Ebola, which has killed 1,013 of 1,848 people infected in four nations. Nigeria and Liberia requested access to ZMapp, Mapp’s experimental antibody therapy, which has been used to treat two Americans who are improving. Spain had obtained ZMapp for a priest who died. Sierra Leone had been awaiting the panel’s conclusion before pursuing ZMapp, said the country’s chief medical officer, Brima Kargbo.

“We’re stuck between a rock and a hard place,” Jonathan Ball, a professor of molecular virology at the University of Nottingham, said in a telephone interview today. “We clearly need to have some kind of intervention, some hope to offer the infected individuals. My concern is that drugs that often work in animals don’t always work in humans.”

Local Narrative

Public health officials to be careful not to lose local populations’ trust when introducing experimental treatments, said Nancy Kass, a professor of bioethics and public health at the John Hopkins Berman Institute of Bioethics in Baltimore.

“It’s really, really important to do nothing to harm the public health system,” Kass said in an Aug. 10 telephone interview. “A narrative that has been prominent in previous epidemics has been, ‘Why are those Americans coming and testing their experimental drugs on us?’”

Lawrence Gostin, director of Georgetown University’s O’Neill Institute for National and Global Health Law, criticized the WHO for not recommending safety testing.

“I do think there needs to be minimal safety testing before we administer experimental drugs,” Gostin said in a conference call with journalists today. “Some drugs can be extremely toxic.”

The experimental treatments have yet to be tested extensively in humans. Some have shown promising results in monkeys.

Boosting Production

San Diego-based Mapp and its partners, Defyrus Inc. and a subsidiary of Reynolds American Inc., are working with the U.S. government to quickly increase production, the company said in an e-mailed statement.

Marie-Paule Kieny, an assistant director-general at WHO, told journalists in Geneva today that she hoped there would be more doses of ZMapp by the end of the year.

“That’s probably the drug that’s likely to have the best safety profile, just because of the way it acts,” Ball said. “It’s a natural antibody, the body’s used to it and you wouldn’t expect too many adverse reactions. Some of the other experimental drugs are a bit more unknown.”

Another option would be to use antibodies from the blood of survivors, 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.

“It might be another alternative to waiting for medicines and vaccines which might not be available,” Heymann said by phone today.

Antivirals, vaccines and blood-based treatments are three types of experimental products that could be used in the outbreak, Kieny said. ZMapp is considered blood-based since it’s an antibody treatment.

Market Failure

“The fact that there is no registered drug for Ebola is a market failure,” Kieny said. “This is a disease of poor people in poor countries where there is no market. This is why there are no stockpiles.”

The use of unproven treatments should be guided by criteria such as informed consent, freedom of choice, confidentiality, preservation of dignity and involvement of the community, the Geneva-based WHO said.

“In the particular circumstances of this outbreak, and provided certain conditions are met, the panel reached consensus that it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects as potential treatment or prevention,” the WHO said in a statement today.

Liberia’s government said today the U.S. has approved its request for sample doses of experimental serum to treat two Liberian doctors. A U.S. government representative will bring the doses to the West African nation later this week.

Small Amount

Providing a small amount of an experimental drug won’t help control the outbreak, said Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases. The focus needs to remain on basic public health and infection-control measures, he said.

“How can a couple of doses control an outbreak with hundreds and hundreds of people?” Fauci said by phone.

U.S. regulators last week said a treatment by Tekmira Pharmaceuticals Corp. could be tested in infected patients, while Mapp’s drug has already been used to treat American aid workers Kent Brantly and Nancy Writebol, who were infected in Liberia. The pair were flown to Emory University Hospital in Atlanta, where relatives and supporters have said they are improving. It remains unclear whether or how much the drug helped.

“I haven’t seen their medical records, but what I have seen reported is that the administration of this drug has had a dramatic and very rapid effect,” the WHO’s Kieny said. It’s “highly probable due to the administration of the drug.”

Spanish Priest

Spain requested the Mapp drug on Aug. 8, after the doctor treating priest Miguel Pajares, a 75-year-old missionary who worked with Ebola patients, asked authorities to help him get it, the country’s health ministry said. The treatment arrived in Madrid the next day, the ministry said. Pajares died today at a hospital in the Spanish capital.

Sierra Leone has approached Tekmira about getting access to its product, Kargbo said in a telephone interview yesterday.

Other companies developing treatments or vaccines for the deadly disease include Fujifilm Holdings Corp. and BioCryst Pharmaceuticals Inc.

Ebola is spread through direct contact with with body fluids, such as blood. The disease is normally treated by keeping patients hydrated, replacing lost blood and using antibiotics to fight off opportunistic infections. The hope is that a patient’s immune system will eventually fight off the virus’s aggressive attack.