Hi sds:
>>I'm begining to see a bearish picture here....<<
It is a bit to early to be bearish, but being concern (for almost all bts) is OK.
Only few note on 2302.
2302 PII trials was to test target validation for ICAM-1(because animal models do not address many questions and they had only 2302 PI in healthy volunteers) and antisense as modulator of ICAM-1. The only way to test drug was i.v. administration in PII trials. Isis got bit lucky with Crohn's and they rushed in to pivotal trials with current i.v. formulation.
Contrary to Crohn's, other trials proceeded at much slower speed.
Now I see current Crohn's trial as *not the best choice*. Not because drug will fail, contrary I think that results will be good. With 300 patients trial is long and expensive, still do not warrant NDA application as treatment drug. Because treatment protocol (dose, how often, period between cycle, remission period,..) was not sure thing from PII trial, more appropriate would be quick and smaller two-three PII trial with several modulation or/and drug formulation. Than large pivotal trials with 2302 or sec.gen. antisense. At this point Isis will need second trial or trials with different formulation/modulation to address patients convenience and drug performance for longer chronic therapy.
Also, I am puzzled why Isis didn't expand current Crohn's protocol with post-trial open label study for patients who responded to drug. To asses drug safety for several therapy cycle and long-term efficiency.
For other indications, 2302 do not have ICAM-1 problems, it is antisense nature. In each of this indication (and potentially others) problems are different and will be solved individually; by drug formulation, mode of administration, sec. gen., ....
All this does not means that I am bearish on 2302, but I do have many questions and will be seeking answers at Open House/SM.
mz |
