ODACDiscussiononAcceleratedApprovalMarch.pptVIP

Ovarian Slides.ppt ODAC Discussion on Accelerated ApprovalMarch 12-13, 2003 DOXIL?(doxorubicin HCl liposome injection) Treatment of Advanced, Metastatic Ovarian Cancer Individuals Available for Questions Sponsor Representatives Martine George, MD Steven Hamburger, PhD Surya Mohanty, PhD April Teitelbaum, MD Margaret Tonda, PharmD Alex Zukiwski, MD Ovarian Cancer Indication Phase IV Status Update Original Phase IV commitment trial (30-49) Completed Planned final survival analysis underway Challenges Surrounding the Phase IV Commitment Trials The time to reach survival endpoint in original Phase IV commitment trial November 1998 Orphan drug designation December 1998 sNDA submitted ovarian cancer indication June 1999: ODAC Meeting and Accelerated Approval sNDA contained data from: 3 Phase II non-comparative studies in relapsed or refractory ovarian cancer (primary endpoint response rate) n = 176 patients Ongoing Phase III DOXIL? vs. topotecan trial (Study 30-49) Data from interim analysis May 1997 First patient enrolled March 1999 Last patient enrolled Phase III Randomized Study of DOXIL? vs. Topotecan in Ovarian Cancer June 2000: Meeting with the FDA after End of Planned Treatment Analysis was provided for Study 30-49 Analysis did not demonstrate superiority in TTP Significant survival advantage of DOXIL? compared to topotecan in the platinum-sensitive group ~50% of patients were alive End of Planned Treatment:Time to Progression End of Planned Treatment:Survival Percent of Patients by Severity of Adverse Events June 2000: Outcome of FDA Meeting for End of Planned Treatment Analysis FDA agreed to a final survival analysis to be performed when a percentage of the 474 randomized and treated patients died or were lost to follow-up 90% events chosen to provide adequate power for survival analysis Protocol amended accordingly A second protocol to prove clinical benefit was required July 2000 ALZA submitted a second Phase IV draft protocol D