Peramivir: Single Dose Prophylaxis for Flu?
By Eric Toner, M.D., October 12, 2005
Dr. Frederick Heydan of the University of Virginia recently presented unpublished data suggesting that peramivir may have the potential for use as single dose parenteral treatment or prophylaxis for influenza (Infectious Diseases Society of America Annual Meeting, San Francisco, October 6-9, 2005). In a talk on the use of antiviral drugs in the setting of an influenza pandemic, Dr. Heydan presented unpublished animal data that suggests that, due to its very long half life, peramivir, an investigational neuraminaidase inhibitor drug, maintains its anti-influenza activity for as long as 10 days following a single intravenous dose.
Peramivir (BCX-1812, RWJ 270201), developed by BioCryst Pharmaceuticals, Inc., has been shown to be more potent in vitro against influenza virus than oseltamivir or zanamivir and has been highly effective in preventing illness due to influenza in mice and ferrets. Peramivir is effective for both influenza A and B.
In phase I and II human trials, peramivir was well tolerated and effective in reducing viral titers when administered orally. Phase III trials commenced in February 2000, but ongoing product development was halted due to relatively poor oral bioavailability and poor market interest in anti-influenza drugs.
Although poorly absorbed orally, animal studies have shown the drug to be very effective in a parenteral preparation. According to BioCryst, an IV/IM preparation is currently in preclinical development. The New York Times recently reported that clinical trials will start this winter.
While full FDA approval will take considerable time, peramivir could be used in the event of an influenza pandemic even prior to FDA licensure under an Emergency Use Authorization (EUA) authority. The EUA authority allows the FDA Commissioner (after consultation with the Director of NIH and the Director of CDC) to approve use of medical countermeasures to diagnose, treat, or prevent serious or life-threatening diseases during an emergency when the totality of scientific evidence available shows that it is reasonable to believe that the product may be effective, that the known and potential benefits outweigh the known and potential risks, and that there is no adequate, approved, and available alternative to the product under consideration.
BioCryst’s CEO, Charles Bugg, was quoted in the New York Times as saying that peramivir is much easier and cheaper to produce than Tamiflu and that 8 million doses could be produced quickly. In 6- 9 months production could be scaled up to 10 million doses per month.
Although parenteral drug administration is certainly more difficult than oral administration, the possibility of prophylaxis with a single dose of drug, particularly if it can be administered IM, makes this an intriguing avenue for further aggressive research. Parenteral therapy has two other benefits, particularly for the critically ill: (1) It can be administered to patients who may not be able to take or absorb oral or inhaled medication and (2) It has been shown to have a significantly faster onset of action compared to currently available neuraminanidase inhibitors.
The staff of the CBN extend warm congratulations to Dr. John G. Bartlett, Associate Editor and a founder of the CBN,
who was recently awarded the IDSA's 2005 Alexander Fleming Award for lifetime achievement at the Society's annual meeting.