Hi Rick, you raise a number of issues here. First, what is the "bcl-2 story"?
In IDEC's 10K it is stated that that a phase II trial for C2B8+CHOP (not clear if as a first-line therapy or if on relapsed patients) achieves 100% response for 30plus patients. I have not heard further reports on this combination, but did notice that a phase II trial for newly diagnosed, intermediate and high-grade NHL patients is underway for the C2B8+CHOP combination at Loyola. Can we estimate when IDEC would file a BLA for this treatment as a first-line therapy? or even for the relapsed population ?
Regarding Coulter's Bexxar, I do not believe their Ab is the mouse version of C2B8; thus, it is not clear if chimeric IDEC's anti-CD20 would share "mouse epitopes" with murine Coulter's anti-CD20. If the respective original mouse Abs are indeed different, then most likely the CDRs are also different, and the constant regions are of course different (human in C2B8, murine in Bexxar) That leaves out the so-called framework regions in the V domains, and not knowing the sequences of the respective Abs, I cannot say much about possible shared mouse epitopes. All this may be mute if the (eventual) labeling for Bexxar asks explicitly to exclude patients that received any mouse or chimeric Ab in the past. Finally, Coulter claims that they expect to file a BLA for Bexxar (for a patient population similar to that being addressed by "naked" C2B8) in the second half of 1998; a pivotal phase II/III trial for Bexxar is in progress with results expected within the next 4-6 months. Bexxar is also in a phase II trial as a first-line treatment; an interim announcement was made last May for ongoing treatment of 17 patients out of a planned total of 60.
In what order do you see the following treatments entering the market ? (of course, all after "naked" C2B8, which should do so in late 97 or very early 98)
from IDEC:
C2B8+CHOP for relapsed, low-grade - finished phase II in 1996
C2B8+CHOP first line, all grades??? - phase II
Y2B8 (murine version of C2B8 radiolabeled with Indium) -phase II?
from Coulter:
Bexxar for relapsed, low-grade - currently in pivotal phase II/II
Bexxar for first-line, low-grade - currently in phase II
from Techniclone:
Oncolym, high and intermediate grades, relapsed or first-line - about to start phase III?
Thanks,
PB |
