Phase 3 results of Genasense plus Dexamethasone in patients with advanced multiple myeloma

Genta Incorporated announced that results from the Company's randomized Phase 3 clinical trial of Genasense(R) (oblimersen sodium) Injection in patients with relapsed or refractory multiple myeloma were presented today at the annual meeting of the American Society of Hematology (ASH) in San Diego, CA.

As previously announced, the trial did not meet its primary endpoint, which was the demonstration of a statistically significant increase in time-to-disease progression.

Patients were eligible for this trial if they had failed standard treatment for myeloma. Two hundred twenty-four patients were randomized to receive standard therapy using high-dose dexamethasone with or without Genasense. The primary objective of the study was to evaluate whether the addition of Genasense would significantly increase the time-to-progression. Secondary end-points included comparisons of objective response, clinical benefit, and safety. Experts that were blinded to treatment assignment made the final determinations of response and progression.

In the trial, 110 patients were randomized to receive Genasense plus dexamethasone, and 114 patients were randomized to receive dexamethasone alone. While randomization achieved a balance in many factors, patients randomized to the Genasense group had significantly lower performance status (P=0.02), which is a measure of general health. Patients in the Genasense group also tended to have a higher baseline measure of serum beta-2-microglobulin (P=0.08), which historically has been one of the most important markers for poor outcome. Prior to entering the study, patients in both groups had received extensive prior treatment with corticosteroids such as dexamethasone (median of 2 steroid-containing regimens).

The median time-to-progression was 3.1 months for patients treated with Genasense plus dexamethasone and 3.5 months for patients treated with dexamethasone alone, which was not significantly different (P=0.26). Sixteen patients (15%) who were treated with Genasense plus dexamethasone achieved a major clinical response (defined as a partial response or a response with greater than or equal to 75% reduction of myeloma protein), compared to 20 patients (18%) who were treated with dexamethasone alone (P=0.6).

Specific adverse events that were significantly higher in the Genasense/dexamethasone group included (but were not limited to) nausea, fever, constipation, diarrhea, and intravenous catheter complications. Serious adverse events that resulted in discontinuation of therapy were equal between the treatment arms (16% for each group). The incidence of Grade 3-4 neutropenia (4%) and anemia (12%) was identical in the two treatment groups. The incidence of Grade 3-4 thrombocytopenia in the Genasense/dexamethasone group was 14% and 5% in the dexamethasone group. Renal failure, which is a common complication in patients with advanced myeloma, occurred with equal frequency -- 3 patients in the Genasense/dexamethasone group and 4 patients in the dexamethasone group. Mortality on study that occurred within 30 days from the last dose of treatment (irrespective of relation to study drugs) occurred in 13 patients treated with Genasense/dexamethasone and 10 patients treated with dexamethasone (P=N.S.). The excess mortality was due to fatal progression of disease (6 patients in the Genasense/dexamethasone group and 1 patient in the dexamethasone group.)

Genasense inhibits production of Bcl-2, a protein made by cancer cells that is thought to block chemotherapy-induced apoptosis (programmed cell death). By reducing the amount of Bcl-2 in cancer cells, Genasense may enhance the effectiveness of current anticancer treatments. Genta is pursuing a broad clinical development program with Genasense evaluating its potential to treat various forms of cancer.