Genta Announces Results of Phase 1 Study Using Genasense Administered by Intermittent Subcutaneous InjectionStudy Shows Safety and Pharmacokinetics Similar to IV Doses in Phase 3 CLL Trial
BERKELEY HEIGHTS, N.J., June 06, 2007 /PRNewswire-FirstCall/ -- Genta Incorporated announced the publication of preliminary clinical results that show the Company's lead anti-cancer drug, Genasense(R) (oblimersen sodium) injection, can be safely administered by intermittent subcutaneous (SC) injection, as well as by brief intravenous (IV) infusion. These regimens may eventually reduce or eliminate the current requirements for administering Genasense by continuous IV (CIV) infusion. The new schedules also expand the potential for use in combination with anticancer drugs that are administered on a daily or weekly basis. The data were published in proceedings of the annual meeting of the American Society of Clinical Oncology (ASCO) that was held this week in Chicago, IL.
The SC study used a new formulation of Genasense that was concentrated 5- fold greater than that used in previous Phase 3 trials. In a dose-ranging pharmacokinetic (PK) and pharmacodynamic trial, bolus SC injections of 75, 150 and 225 mg yielded dose-proportional plasma concentrations that were associated with down-regulation of Bcl-2 in blood cells. The 225 mg dose level achieved exposure PK parameters that were similar to levels achieved at the 3 mg/kg CIV daily dose level that was tested in the recent Phase 3 trial of Genasense in chronic lymphocytic leukemia (CLL).
A second phase of the program is testing escalating doses of Genasense administered as a 2-hour IV infusion. Single 150 mg doses, as well as repeated 150 mg doses administered daily for 5 consecutive days, have been well-tolerated. To date, the principal adverse events have been reversible skin reactions at the injection site on the SC schedule and transient fever on the brief IV schedule.
"These highly encouraging data represent important next steps that may greatly improve dosing convenience for patients," commented Dr. Raymond P. Warrell, Jr., Chairman and CEO of Genta. "We are continuing dose escalation in the brief IV schedule and hope to incorporate these regimens into future studies using new agents that are administered on daily or weekly schedules."
Preclinical studies have demonstrated that high-dose intermittent treatment with Genasense was associated with increased uptake of the drug within tumors and yielded superior efficacy when combined with paclitaxel, temozolomide, (Temodar(R); Schering Plough, Inc.) and multiple kinase inhibitors (erlotinib, imatinib, sunitinib, and sorafenib) in a highly aggressive model of malignant melanoma.
Posted: June 2007