H1N1 COUNTERMEASURES STRATEGY AND ... - PHE Home

NBSB Pandemic Influenza Working Group
Detailed Report
Dr. Hayden listed a number of anti-influenza agents that are being investigated. A March
2009 meeting of NIAID, BARDA, and others focused on new agents (the meeting
summary is available), including host-directed approaches. There is potential for
development of topical single-dose CS8958; it is in phase-2 trials, but no data have yet
been reported. One new agent by Toyama, Favipiravir (T-705), targets polymerase. It
has better in-vitro activity than ribavirin. Phase-2 trials of efficacy have been completed
in Japan. The drug appears to have oral bioavailability, and Dr. Hayden called it
interesting. The other drugs are all in phase-1 trials, and delivery issues are being
addressed.
Of the new agents, several have antibodies that target group-1 hemagglutinins. There is
potential inhibition by monoclonals that direct to specific areas. Model data show doserelated
improvements in survival and efficacy.
Conducting clinical studies in hospitalized patients is very hard, Dr. Hayden noted. More
effective diagnostic tools are needed. Hospitalized patients are a heterogeneous group;
they have co-morbidities, co-infections, concomitant therapy, variable disease courses
and pathogenesis, and many have exacerbation of underlying disease. Researchers face
recruitment and trial design hurdles, e.g., getting informed consent from impaired
patients, determining inclusion and exclusion criteria to get generalized data, and
incorporating changing standards of care. According to the FDA draft document out for
comment, investigators need to closely consider the endpoints of their studies. Also,
there is a lack of experienced investigators and staff.
A study in hospitalized patients is trying to address the issue of endpoints. It is a
randomized, controlled trial comparing oseltamivir and peramivir, which measures time
to clinical stability and time to return to daily activity.
Dr. Hayden summarized the issues of concern for antiviral treatment:
Medical need exists for parenteral agents for seriously ill patients, novel agents
with new antiviral spectra, and new agents with less frequent dosing
requirements.
SNS diversification is warranted.
Realistic development pathways are needed for new agents, especially
combination therapy for hospitalized patients. Development would be enhanced
by use of endpoints that are antiviral-oriented and a domestic hospital-based
network for severe acute respiratory illness (SARI) studies.
Dr. Pavia commented that progress on new antiviral agents has been distressingly slow
despite all the attention to pandemic influenza in the past 5 years.
GSK Zanamivir Strategy and Response to Novel H1N1— Judith Ng-Cashin, M.D.
Dr. Ng-Cashin said GSK recognizes the need for antivirals and is working to deploy its
existing stockpile supplies, and rapidly maximize its production of its approved product,
Relenza Rotadisk/Diskhaler. GSK is also investing in an alternative strategy to increase
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