Genasense CLL Trial Meets Primary Endpoint, But Survival Benefit Not Yet Shown

Genta believes that the lack of a survival benefit seen in a Phase III trial of Genasense in chronic lymphocytic leukemia reflects the relatively short follow-up time available for analysis, CEO Raymond Warrell said during a Nov. 9 earnings call.

"As of the data cut-off date, we had not yet observed a significant difference in certain key secondary endpoints, including time to progression and overall survival," Warrell said. "In part, the ability to detect these differences was limited by the relatively short duration of follow-up."

"We are continuing to analyze these and other secondary endpoints, and we should have more information available next month," he said. The full study results are expected to be presented at the American Society of Hematology annual meeting in San Francisco Dec. 4-7.

Genta released what it described as "key headline results" from the CLL study on Nov. 8, the same day it announced that Sanofi-Aventis is terminating its collaboration agreement for the oncologic (see ¹ (Also see "Sanofi-Aventis Drops Genasense After Genta Declines To Modify Deal" - Pink Sheet, 9 Nov, 2004.)).

In the study, 241 relapsed or refractory CLL patients were randomized to standard chemotherapy (fludarabine and cyclophosphamide) with or without Genasense.

"The primary objective of the study was to evaluate whether the addition of Genasense would increase the proportion of patients who attained major objective responses (defined as complete remission or a nodular partial remission)," the company said.

The Phase III study met the primary endpoint, Genta said. "This endpoint was chosen because multiple prior studies have shown that the ability to achieve these so-called CRs and NPRs, and quite unlike partial responses or PRs, has been clearly linked to increased survival in patients with CLL," Warrell said.

Nevertheless, the inability to demonstrate an outright survival benefit could prove troublesome for Genta.

In May, FDA's Oncologic Drugs Advisory Committee concluded that Genasense failed to show a "real effect" on progression-free survival in malignant melanoma. Genta and Sanofi withdrew the melanoma NDA after the negative ODAC review.

Genta later said it hoped to submit an NDA for either a CLL or multiple myeloma indication by year-end.

"Genta plans to discuss the feasibility of submitting an NDA based on" the Phase III CLL data with FDA, the company said.

The trial showed a greater incidence of serious adverse reactions among patients taking Genasense.

"The incidence of certain serious adverse reactions, including but not limited to nausea, fever and catheter-related complications, was increased in patients treated with Genasense," the company said. "Reactions leading to death that were specific to the Genasense treatment group included single episodes of renal failure, 'cytokine release reaction,' and tumor lysis syndrome."

Phase III data for a myeloma indication also are expected to be presented at the ASH meeting in December.

In addition, data from Phase III from studies in non-small cell lung cancer and small cell lung cancer are expected to be available in 2005, the company said.

- Sue Sutter