DR. FINEBERG: Let me ask a question of the group who were reporting on the development of antivirals. The timeframes of that set of studies struck me that one would really have to look quite concretely and specifically at the state-of-science for each line of activity that one is thinking about. I wonder if anyone in that group could comment to help us understand where, if the group did discuss this, the most promising direction of development might rest today, and where things were still at a much more speculative stage across that list that we saw arrayed.

PARTICIPANT: As everybody is aware, there is a relative—and I just say relative paucity of drugs in the pipeline that are unique and different for the treatment of influenza infection. There are several that are available, but they have not been studied appropriately in high risk patient populations. We have tried to emphasize that, and quite honestly, it can be done immediately. That includes evaluating drugs like oseltamivir in infants less than 1 year of age.

There is a fundamental problem that we have, and that is the pre-clinical animal toxicity data would imply that oseltamivir is toxic for the newborn brain in a rat model. We have to understand how we can circumvent that problem. And if we can not, we have to find a back-up drug such as peramivir. Peramivir has gone through phase 3 studies. It is not orally bioavailable. It can be given parenterally. It is available for a group to develop as quickly as possible. After that, then it becomes a question of the long acting neuraminidase inhibitor applied topically, or alternative strategies. But there are clearly two or three clinical protocols that could be developed and implemented within a short period of time.

PARTICIPANT: These drugs are available and could be studied in next influenza season. There are other possible approaches that presumably in the next year or two could be undertaken with regard to looking at resistance emergence strategies to reduce the combination therapies with antivirals. Another point of discussion within our group was the need to start studies of the available drugs to determine their impact, and their dose-related impact on some of the important outcomes in H5 disease in South Asia.

DR. FINEBERG: Yes, I thought that point was really quite telling, as well as some of the others that emphasized the importance of proactive planning for clinical protocols at the time outbreak would occur. We learned the lesson from SARS on how valuable it would have been to have had those protocols in place, accepted and ready to go across a whole spectrum of geographic locations. I think that is something that could definitely be done in a short timeframe, and in preparation for the next flu season.

There is relatively little, as one looks at the list that we have arrayed so far, that actually would have a bearing on something that happens in the next 12 months. And I think the reality of all of us in thinking about the importance of a research strategy is ultimately to work it back to what we can do in what timeframe to provide the kind of preparation, preventive and ameliorative strategies that we all know are going to be needed.

The discussion that we have had is of course premised on the great worry of the grand pandemics. But a lot of what we are talking about truly is going to be relevant year after year to endemic influenza that is still underappreciated as a significant source of mortality and morbidity in countries all around the world. So, I think there will be a true value coming out of this discussion, even if we are fortunate to not experience for some time, any of the greatest threats that worry us.



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