Genta Incorporated (OTCBB: GNTA) provided a comprehensive update of its Research and Development programs this week in conjunction with the Company’s presentation at the Biotech Showcase in San Francisco today.
Genasense® (oblimersen sodium) Injection
As one of the founding antisense companies, Genta has initiated and completed more randomized Phase 3 trials with these compounds than any other company. Genasense, the company’s lead oligonucleotide compound, targets a central regulatory protein in a network of cell death molecules, known as Bcl-2. Over-expression of Bcl-2 is a common feature of many types of human cancer. Extensive preclinical data have shown that targeted reduction of Bcl-2 with Genasense can amplify the effectiveness of many types of cancer therapy.
Genta has completed accrual into two randomized Phase 3 trials of Genasense in patients with advanced melanoma, known as GM301 and AGENDA, respectively. Two-year followup of GM301 showed that patients treated with Genasense plus chemotherapy achieved statistically significant improvements in early endpoints of overall response and progression-free survival (PFS), but that the primary endpoint of overall survival (OS) was not significantly superior (P=0.077). Extensive analysis of GM301 showed that patients who derived maximum survival benefit in the Genasense group were characterized by low-normal levels of the tumor biomarker, lactate dehydrogenase (LDH).
AGENDA was designed similarly to GM301 with only a few differences: eligibility was limited to patients with low-normal LDH; a placebo was employed to maintain a double-blind design; co-primary endpoints included PFS and OS; and survival was captured on all patients up to 2 years from entry of the last patient. Early endpoints from AGENDA again showed improvements for patients treated with Genasense plus chemotherapy, but the differences were not statistically significant. A futility analysis conducted by the independent Data Monitoring Board, based on approximately 50% of projected mortality, indicated that the conditional probability to observe the originally projected OS difference exceeded 50%. The Company currently projects a total mortality of approximately 250 events by the end of the study, which yields an overall statistical power for the study of approximately 84%. (Please note that
of these calculations reflect the likelihood of achieving a positive or negative result. They refer only to the likelihood of observing a statistically significant result [P ≤ 0.05] with the originally assumed difference [i.e., a hazard ratio for OS = 0.69].)
Followup for determination of the late endpoints of durable response (i.e., ≥ 6 months duration) and overall survival will conclude on March 31, 2011. Release of these data is anticipated in early Q2 2011. If the survival result is positive, the Company envisions filing a New Drug Application (NDA) to the Food and Drug Administration (FDA) during 2011.