Dear George,
A year or so ago I mentioned to you that I though the mortality for meinigococcemia was more in the
10-15% range, rather than the frequently mentioned 20-30%. I thought that it would be more difficult for
Neuprex to show efficacy against a significantly lower mortality percentage.
Following the DSMB meeting in the Fall of 98, Xoma stated that safety was not an issue and that the trial
would continue. They also alluded to the possibility of making changes to the PIII, after the DSMB
meeting in late 98 or early 99. At the time that statement seemed strange to me, I thought, “How could
they possibly make significant changes to a PIII trial as it was approaching conclusion.”
Now consider this scenario; let's say that either officially or unofficially Xoma has been carefully tracking
bacterial endotoxin load for each patient utilizing their proprietary LPS assay. Let's also assume that it is
clear that the children receiving Neuprex have dramatically lower circulating endotoxin and hence much
lower morbidity, but the overall mortality is not significantly different. (Due to the best pediatric intensive
care for meinigococcemia in the world at St. Mary's in London) Xoma would be caught between a rock
and a hard place, on the one hand they can see that Bpi is binding and inactivating the endotoxin, but that
is not the endpoint, mortality is. Assuming this is true, I can see where Xoma might want to approach the
FDA and ask for a change in the endpoint from mortality to dramatic reduction in circulating endotoxin.
This dream is all my own, I submit it only for review and comment. |
