Encouraging results reported for injectable flu drug

Robert Roos

Oct 31, 2008 (CIDRAP News) BioCryst Pharmaceuticals Inc. reported encouraging results this week in two phase 2 trials of its injectable antiviral drug, peramivir, a potential new treatment for influenza.

Peramivir is a neuraminidase inhibitor, like the licensed antivirals oseltamivir (Tamiflu), which is taken orally, and zanamivir (Relenza), inhaled as a powder.

In one study, a single intravenous (IV) dose of peramivir in outpatients ill with flu reduced the duration of their symptoms by about 22 hours compared with a placebo group, a statistically significant difference, according to BioCryst, based in Birmingham, Ala.

In the other trial, hospital patients who were seriously ill with flu were treated for 5 days with either IV peramivir or oseltamivir, with similar results in both groups, including no deaths and a median of 4.0 days to hospital discharge, the company said.

Neither set of results has yet been published in a peer-reviewed journal. The company described the inpatient study in a press release and a teleconference on Oct 27; the outpatient study was reported in an Oct 28 press release and a poster presentation at the 46th Interscience Conference on Antimicrobials and Chemotherapy/Infectious Diseases Society of America (ICAAC/IDSA) meeting this week in Washington, DC.

The new findings come 13 months after the company reported disappointing results in an earlier phase 2 trial of the drug. In that study, flu patients who received injections of peramivir did better than a placebo group, but the difference was not significant. The company said at the time that the use of shorter needles than were used in an earlier trial probably resulted in inadequate doses.

Outpatient findings
The outpatient study was sponsored and conducted in Japan by Shionogi & Co. Ltd., which in 2007 bought from BioCryst the rights to develop and market peramivir in Japan.

The study involved 296 patients who tested positive for influenza within 48 hours after symptom onset, BioCryst reported. The volunteers were divided into three groups, with 99 receiving 300 milligrams (mg) of peramivir IV, 97 receiving 600 mg of the drug IV, and 100 receiving an IV placebo.

The primary end point was time to alleviation of symptoms, which was 81.8 hours for the placebo group. The respective times for the 300-mg and 600-mg peramivir groups were 59.1 and 59.9 hours, both of which were significant reductions, the company said.

In addition, both peramivir groups had significant improvements in a composite symptoms score, starting as early as 24 hours after treatment, the statement said. The drug was well-tolerated, with adverse-event profiles similar for the treatment and placebo groups.

"This phase 2 study was a critical test of peramivir, which demonstrated for the first time that a single administration of this potent neuraminidase inhibitor can be effective in treating seasonal influenza," Dr. William P. Sheridan, chief medical officer of BioCryst, said in the news release.

Hospital study
The inpatient study was designed primarily to assess how long it would take patients with serious or life-threatening flu to become clinically stable with 5 days of treatment with peramivir or oseltamivir. The study was conducted at centers in the United States, Canada, Hong Kong, Singapore, Australia, New Zealand, and South Africa.

Clinical stability was a composite measure based on temperature, oxygen saturation, respiratory rate, systolic blood pressure, and heart rate. For ethical reasons, the study included no placebo arm.

The investigators enrolled 122 patients who had flu confirmed by polymerase chain reaction. Of these, 41 received 75 mg of oseltamivir twice daily, 41 received 200 mg of IV peramivir twice daily, and 40 received 400 mg of IV peramivir twice daily.

"The time to clinical stability was 25.3 hours for all groups combined, with no statistically significant differences across treatment groups," Sheridan reported during the Oct 27 conference call (a recording of which is available online).

Secondary outcomes for all groups included no mortality, no clinical relapse, a median of 4.0 days to hospital discharge, and a median of 10.8 days to resumption of normal activities, the company reported.

Sheridan said no significant differences in any of the efficacy end points were seen, which "was expected given the active control, small sample size, and exploratory phase 2 nature of this study."

In response to questions, he said the study was not designed to show differences between peramivir and oseltamivir. He said peramivir is important because it permits parenteral treatment of flu patients, adding, "At the ICAAC meeting the need for a parenteral drug for influenza has come up several times already. Also there's concern about resistance to existing drugs, including oseltamivir."

Sheridan also said that the zero mortality in the study is "an important finding worthy of follow-up," given that a previous epidemiologic study showed a mortality rate of 10% in 219 patients who were not treated with neuraminidase inhibitors.

In the news release, Dr. Michael Ison of Northwestern University, principal investigator in the study, said, "This landmark study provides us great insight into the course of treatment for patients who are hospitalized for influenza. The results indicate a potential role for antiviral therapy, which is critical as currently there are no antivirals approved for patients hospitalized for acute serious or potentially life-threatening influenza."