Biotech Values

[rancherho]

1. Taxotere (docetaxel) has been the standard of care and the only therapy to have demonstrated increased median survival (2.4 months in its TAX327 pivotal trial) in AIPC/HRPC since the FDA approved its use in May 2004.http://content.nejm.org/cgi/content/full/351/15/1502

2, The Provenge 9901 and 9902a trials commenced enrollment in 2000. The crossover protocol allowing control patients to take the lower dose of Provenge processed from frozen and thawed immune cells upon progressionwas before FDA approval of docetaxel but after Ph2 testing showing that Provenge was safe and well tolerated and increased Time to Progression. Crossover protocols were also allowed in the Tax327 trial and in the 160 patient Ph3 pivotal trial that lead to FDA approval of mitoxantrone and prednisone (the control arm in Tax327)for palliation of symptoms in 1996. Docetaxel use after GVAX, of course, proved beneficial in the GVAX Ph2 trials, which took place long after the Provenge Ph2 trials.

3. As a general rule in all cause survival studies, patients cannot be censored once randomized. There is also a significant question as to whether it is ethical to withold standard of care tretment once an experimental treatment protocol had been completed. Provenge's 9901, 9902a and 9902b trials as well as the GVAX Vital-1 trial aim for approvals in asymptomatic AIPC/HRPC. Since docetaxel is the standard of care in the later symptomatic stage, there should be no problem with earlier Provenge or GVAX (both have protocol limitations on prior use of chemos). Also, while Drs. Small and Petrylak noted the use of docetaxel after Provenge, no records were required of the cycles/dosing used. Finally, there would be little reason to rule out either immunotherapy as succesful "pre-adjuvants" (prequel/sequel?)to the docetaxel standard of care.

4. As for 9901 and 9902a and CD54 ranges, you should review the slides and transcripts of DNDN's Dr, Provost's 2/06 presentation to the CTGT AC at: http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4205T1.pdf
and
http://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4205s1.htm
Hope this is helpful.