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New Injectable Drug Peramivir Is as Effective as Oseltamivir (Tamiflu) for Seasonal Influenza

A single intravenous injection of the new flu drug peramivir worked as well as the widely used oral agent oseltamivir (Tamiflu) for relieving symptoms of seasonal influenza, according to 2 presentations at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009) last week in San Francisco. While these studies did not involve the novel H1N1 "swine" flu, peramivir works the same way as agents that are active against the new virus.

Peramivir is an investigational influenza neuraminidase (NA) inhibitor, in the same class as the approved flu drugs oseltamivir and zanamivir (Relenza). Blocking the activity of neuraminidase interferes with flu virus replication, and is thought to work by preventing newly formed virus particles from "budding" out of a host cell.

In the first study, researchers from Shionogi and Co. in Japan investigated the inhibitory effect of peramivir against avian (bird) influenza viruses both in vitro and in vivo. In laboratory cell cultures and in mice, peramivir strong inhibited neuraminidase activity and replication of various highly pathogenic bird flu strains.

The therapeutic effect after a single dose of peramivir was comparable to that of repeated doses of oseltamivir or zanamivir for 5 days; when peramivir was given for 5 days, its effectiveness was greater than that of the other 2 drugs used for the same duration.

In the second presentation, investigators with the S-021812 Clinical Study Group described a trial evaluating a single intravenous dose of peramivir versus oral oseltamivir for treatment of acute, uncomplicated seasonal influenza in an outpatient setting.

A previous Phase 2 placebo-controlled trial in Japan demonstrated that a single dose of peramivir was effective in patients with acute influenza, the researchers noted as background.

The present Phase 3, double-blind, non-inferiority study included 1099 patients in Japan, Korea, and Taiwan who had positive influenza rapid antigen tests. Participants were randomly assigned to 3 groups, receiving either a 300 mg or a 600 mg single-dose intravenous infusion of peramivir, or else 75 mg oral oseltamivir administered twice-daily for 5 days. Treatment was started within 48 hours after the first symptoms; individuals with severe symptoms were excluded.

In an intent-to-treat analysis, the median time to alleviation of symptoms was similar in the 300 mg peramivir arm (78.0 hours), the 600 mg peramivir arm (81.0 hours), and the oseltamivir (arm (81.8 hours), demonstrating that peramivir, at either dose, was non-inferior to oseltamivir. Furthermore, patients taking peramivir had their fever return to normal significantly faster than those taking oseltamivir.

Peramivir worked against seasonal flu strains that were resistant to oseltamivir. The rate of adverse drug reactions was significantly lower in the 300 mg peramivir arm than in the oseltamivir arm, due to fewer gastrointestinal symptoms.

The investigators concluded that, "A single intravenous administration of peramivir could be an alternative to oseltamivir to treat patients with acute influenza."

While oral agents are often preferred to injected drugs in terms of long-term tolerability and convenience, a single-dose injection may be favored over taking a drug for several days. Furthermore, gastrointestinal symptoms of influenza (e.g., vomiting and diarrhea) may make it difficult to effectively use an oral medication.

Researchers are speeding up research on drugs they hope will be effective against the 2009 H1N1 "swine flu," which is now at pandemic levels and expected to spread further during the North American fall/winter flu season.

This study was conducted during the 2008-2009 flu season, before the emergence of the novel H1N1 strain. However, the new flu strain is susceptible to neuraminidase inhibitors including oseltamivir and zanamivir -- in fact, a non-approved injectable formulation of zanamivir has recently been used as a rescue therapy for people with severe symptoms -- suggesting that peramivir will also likely be effective.

Peramivir currently has FDA "Fast Track" status in the U.S., and is being developed by BioCryst Pharmaceuticals.

9/22/09

References

M Kobayashi, M Kodama, R Yoshida, and others. Inhibitory Effect of Peramivir (S-021812, BCX-1812) against Highly Pathogenic Avian Influenza Viruses. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco. September 12-15, 2009. Abstract V-1064.

S Kohono, MY Yen, HJ Cheong, and others. V-537a - Single-Intravenous Peramivir vs. Oral Oseltamivir to Treat Acute, Uncomplicated Influenza in the Outpatient Setting:A Phase III Randomized, Double-Blind Trial. V-537a. ICAAC 2009. Abstract V-537a.