Division of Oncology Drug Products Presentation NDA 21-649 Genasense (Oblimersen) for metastatic melanoma ODAC May 3, 2004. Project Management Nicholette Hemingway, MPH Medical Review Robert Kane, MD Ann Farrell, MD Statistical Review Peiling Yang, Ph.D.
Nicholette Hemingway, MPH
Robert Kane, MD
Ann Farrell, MD
Peiling Yang, Ph.D.
Rajeshwari Sridhara, Ph.D.
Lilliam Rosario, Ph.D.
David E. Morse, Ph.D
Haripada Sarker, Ph.D.
Hasmukh Patel, Ph.D.
Gene Williams, Ph.D.
Brian Booth, Ph.D.FDA Review Team for Genasense (G3139)
Response Rate (RR) = 23% (6%CR)
Survival times range 5 – 9 months
Progression-free Survival (PFS) benefit for DTIC
No evidence for survival advantage for any combination over DTIC alone
therapy of melanoma
DTIC IV each 3 weeks
versus TMZ p.o. each 4 weeks
(for patients assigned to G + DTIC)
Using the protocol specified analysis with the ITT population, no survival benefit was demonstrated by adding Genasense to DTIC treatment versus DTIC alone.
Progression-Free Survival (PFS)
Is this a true finding?
Survival Event Date
PFS Event Date
= Date of Death or actual tumor progression
Impact of systematic bias:
The claimed PFS benefit may not be a true finding because of:
≥ 6 months as a durable response.
clinical benefit for metastatic melanoma
2. Response rate:
3. Durable response rate: No sig. difference (3.4% (G+DTIC) vs. 1.3% (DTIC alone))
4. Response duration: 126 days (G+DTIC) versus 127.5 days (DTIC alone)
5. Performance status:
- No benefit observed from Genasense
6. Symptomatic benefit: Not observed
7. Safety: Greater toxicity for the combination of G + DTIC