Injectable drug seen as potential treatment for flu, both seasonal and avian

Oct 2, 2006 (CIDRAP News) – Recent tests suggest that an antiviral drug given by intravenous (IV) or intramuscular (IM) injection could eventually serve as another weapon against influenza, according to results presented at a conference last week.

In animal studies, peramivir improved survival in mice and ferrets infected with H5N1 avian flu, according to a news release from BioCryst Pharmaceuticals Inc., Birmingham, Ala., which is developing the drug. The results were presented Sep 30 at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco.

In addition, in phase 1 clinical studies, IV and IM doses of peramivir produced high blood levels of the drug in human volunteers without causing any adverse events, according to Dr. Charles E. Bugg, PhD, chairman and chief executive of BioCryst.

The clinical studies "showed you can achieve high blood levels in humans safely," Bugg told CIDRAP News in an interview today. The combination of those results with the animal studies is promising, he said.

Peramivir is a neuraminidase inhibitor, like the licensed antivirals oseltamivir (Tamiflu), and zanamivir (Relenza). Oseltamivir is an oral drug, while zanamivir is inhaled as a powder. Many countries have stockpiled oseltamivir on the assumption that it will help if the H5N1 virus sparks a pandemic.

BioCryst started developing peramivir in 1998 in partnership with Johnson and Johnson, Bugg said. Early studies showed the drug inhibited flu viruses effectively, but when taken orally, its bioavailability was very low, which prompted Johnson and Johnson to pull out of the program.

Because injectable peramivir looked promising in animals, the program was resurrected with help from the National Institutes of Health about a year ago, Bugg said. He explained that the company is developing an IV formulation intended for hospital patients and an IM formulation for outpatients.

In the animal studies, four groups of mice were infected with an H5N1 virus and then were treated with either a single IM injection of peramvir, five daily IM injections, oral oseltamivir for 5 days, or an IM placebo injection daily for 5 days, according to the news release. The single-injection group had a 70% survival rate and the five-injection group a 80% survival rate, compared with 36% for the placebo group and 70% for the oseltamivir group.

In the ferret experiment, one group received a daily IM injection for 5 days, while a second group received an IM placebo daily for 5 days. Eighty-six percent of the treated group survived, versus 43% of the placebo group, according to the news release.

Bugg said treatment was started an hour after the animals were infected with the virus. He said additional studies will involve longer time lapses between exposure and the start of treatment.

Results of the clinical studies were presented by flu expert Frederick Hayden, MD, of the University of Virginia. Three groups of volunteers received different IV doses of peramivir, and a fourth group received increasing IM doses once a day for 3 days, the company release said. "Preliminary safety results indicate that in the four studies, all doses were well-tolerated with no adverse laboratory events or ECG findings reported," the statement said.

"I think peramivir looks very promising," said Hayden, as quoted in a Sep 29 Bloomberg News report. "It's proven to have very good activity in single doses."

In an interview, Hayden told Bloomberg that injecting peramivir into the bloodstream or into muscle can produce blood levels 100 times higher than those seen with oral oseltamivir, now considered the most promising treatment for H5N1 infection.

Last January the Food and Drug Administration (FDA) gave injectable peramivir fast-track status for regulatory approval, according to BioCryst. But Bugg said it would take at least several more years to gain FDA approval.

"We'll do a clinical trial this flu season, and then two more next season," he said. "We're looking at several more years." He said the company will be meeting with the FDA soon to review the program and may have a better idea of the timeline after that.

Bugg said plans also call for testing the drug in human H5N1 patients at sites in Thailand and Vietnam and also to make it available in Turkey, which had human cases early this year.

"We'll be trying to collect data from H5N1-infected patients in Southeast Asia in collaboration with the World Health Organization," he said. "We'll be on the front line to capture H5N1 if it occurs. But realistically we won't have enough [patients] for a meaningful statistical analysis."

In a Sep 29 Reuters report, Bugg said peramivir is easier to make than Tamiflu. One Swiss manufacturer can make 1 metric ton of the drug in a month, enough to treat an estimated 8 million people, he said.

See also:

Oct 2 BioCryst release on peramivir
http://investor.shareholder.com/biocryst/releasedetail.cfm?ReleaseID=213054

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