To Those Who Have an Interest IN BTRN, the following is a post from a well informed poster on Yahoo. By melding what Soldier posts on Yahoo and what the "Main Man" Rick posts here on SI you can get a good understanding of the scientific issues behind BTRN.
Re: SI board---Psoriasis strategy
by: soldier30
Long-Term Sentiment: Strong Buy 11/11/01 01:02 am
Msg: 1278 of 1281
For some reason, I can't post on SI even though I'm a member--??
I wanted to address concerns raised about 507 on SI--it's argued that the IV data do in fact, show efficacy even at the incredibly small, non-depleting dose of .0012 mg/kg --yet, MEDI has focused only on the T-cell depleting doses--I have reviewed the posters over and over again and agree with Rick's conclusions:
a) in the IV trial, there is equivalent efficacy between .0012, .012 and .04--mean PASI reductions are about 40% at Day 140 (final dose was at day 49)--believe it ot not, the mean PASI reducion appears to be 42% for .0012 and 38% for .04!!
b) there does not, therefore appear to be a dose-response
Rick's point therefore is brilliant , as always, and one must then ask a host of questions:
1-why does the efficacy seem great at these tiny non-depleting doses in the IV study but clearly not in the SC study?
2-why is it that despite the equivalence (if not trend toward superiority ) in mean PASI score not translate into an equivalence among the endpoint of: percentage attaining PASI 75--here, only 1 of 6 at .0012 hits PASI 75 while 3 of 6 at .04 hit PASI 75?--
Here a few theories as to why MEDI focuses on the high-dose groups --
a) simple theory--the bottom line is that PASI 75 is everything and only 1 of 6 patients at .0012 IV achieved PASI 75 --since SC is the more convenient mode of administration AND the PASI75 issue favors the high-doses, MEDI chose to go with that emphasis
b) mystique theory--MEDI may have uncovered a fundamental difference between IV and SC administration (? some diff. in impact on T-cell trafficking)--without tipping their hand , they are planning an IV program with non-T-cell depleting doses but only emphasizing the T-cell depleting doses in their release to throw off Biogen
c) fluke theory--since the n's are so small for each dosage group, MEDI isn't sure whether to believe the astounding .0012 data and therefore dismissed it or seeks to confirm it in the Phase II--
My personal view: MEDI is smarter than they would have people believe--I think Mott has played the game very cleverly until now (for reasons I can't get into ...) and he will pull off a masterful coup with psoriasis |
