Program Schedule

1171
The development of influenza virus variants with reduced susceptibility following peramivir treatment: an analysis of clinical and post-marketing experience

Session: Poster Abstract Session: Viral Infections: Treatment and Prevention
Friday, October 10, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Posters
  • ID Week peramivir virology poster final 2014_10_01.pdf (188.2 kB)
  • Background: Peramivir is a neuraminidase inhibitor (NAI) with potent in vitro activity against all virus sub-types. It has been commercially available in Japan since 2010 and to date more than 1 million patients have received peramivir following approval. Influenza A/H1N1 viruses containing an H275Y mutation in the neuraminidase gene that confers resistance to oseltamivir have been previously shown to result in reduced sensitivity to peramivir.

    Methods: The peramivir clinical development program included over 2,800 subjects with laboratory-confirmed influenza infection in 10 phase 2 and 3 studies. The activity of single dose peramivir treatment in the outpatient setting and repeat dose treatment in hospital studies was evaluated. Phenotypic analysis of paired baseline/ post-treatment virus isolates was attempted for all subjects with culturable virus and genotypic analysis of the NA gene (and hemaglutinin [HA] gene in a subset) was conducted on viruses from subjects with prolonged virus shedding or with increased 50% inhibitory concentration (IC50) for peramivir. A surveillance study conducted in Japan since 2010 assessed the prevalence of circulating strains with resistance to peramivir.

    Results: Baseline 50% inhibitory concentration (IC50) data was available for over 2300 subjects. Over 1200 subjects were selected for sequence analysis, and partial or complete sequence data was available for 1122 subjects.  The only treatment-emergent mutation associated with peramivir exposure detected in more than 1 subject was an H275Y mutation in influenza A/H1N1, which was identified in 13 subjects. Data from postmarketing surveillance in Japan following the approval of peramivir (RAPIACTA™) have identified no novel mutations in circulating seasonal influenza strains that are associated with loss of susceptibility to peramivir.

    Conclusion: Loss of sensitivity to peramivir in clinical isolates appears to be associated primarily with development of an H275Y mutation in the NA gene. The incidence of development of treatment-emergent H275Y substitutions in response to treatment with peramivir appears to be low.

    Phil Collis, PhD1, Paul Zoeteweij, PhD2, Hans Bunschoten, PhD2, Ray Taylor, MBA1, YS Babu, PhD3 and William Sheridan, MB BS1, (1)BioCryst Pharmaceuticals, Durham, NC, (2)Viroclinics Biosciences, Rotterdam, Netherlands, (3)BioCryst Pharmaceuticals, Birmingham, AL

    Disclosures:

    P. Collis, BioCryst: Employee and Shareholder, Salary

    P. Zoeteweij, BioCryst: Research Contractor, Research support

    H. Bunschoten, BioCryst: Research Contractor, Research support

    R. Taylor, BioCryst: Employee and Shareholder, Salary

    Y. Babu, BioCryst: Employee and Shareholder, Salary

    W. Sheridan, BioCryst: Employee and Shareholder, Salary

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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