Sunesis Pharmaceuticals presents data of Voreloxin in patients with acute myeloid leukemia and ovarian cancer

Sunesis Pharmaceuticals, Inc. presented data from three clinical trials of the company's lead drug candidate, voreloxin (formerly SNS-595), at the Chemotherapy Foundation Symposium held in New York on November 4-8.

Data previously presented from Phase 1 and Phase 1b/2 studies in patients with acute myeloid leukemia (AML) showed that preliminary clinical responses were observed in the relapsed/refractory AML population and the data supports further clinical development for voreloxin both as a single agent and in combination with cytarabine. Preliminary efficacy results previously presented from an ongoing Phase 2 trial demonstrate single agent activity of voreloxin in advanced platinum-resistant ovarian cancer and that the drug is generally well tolerated in this difficult-to-treat patient population.

"We believe that voreloxin has the potential to change the standard of care in AML and platinum-resistant ovarian cancer and look forward to reporting updated results of our AML trials at ASH," said Daniel Swisher, Chief Executive Officer, Sunesis Pharmaceuticals. "Our goal is to advance voreloxin into a pivotal trial in AML by the end of 2009."

Phase 1 and 1b/2 Studies of Voreloxin in AML

Data presented from a completed Phase 1 dose escalation trial of voreloxin as a single agent in acute leukemias (N=73) showed that single agent voreloxin was generally well tolerated, with the most frequently observed dose limited toxicity (DLT) being reversible grade 3/4 oral mucositis. The researchers concluded that single agent activity in the relapsed/refractory AML population supports further clinical development.

Researchers also presented initial data from an ongoing Phase 1b/2 study testing voreloxin in combination with cytarabine. The Phase 1b/2 trial is designed to evaluate safety, pharmacokinetics and anti-leukemic activity of escalating doses of voreloxin when administered on days one and four with a fixed dose of 400 mg/m2/day of cytarabine given as a continuous infusion for five days.

Of 11 evaluable patients in the first three cohorts, 3 patients have achieved a complete remission (one at 20 mg/m2 of voreloxin and two at 34 mg/m2 of voreloxin). Six patients were enrolled in cohort 4 (50 mg/m2 of voreloxin) and one had complete remission and one had a complete remission without full platelet recovery.

A Phase 2 Trial of Voreloxin in Platinum-Resistant Ovarian Cancer

In this ongoing Phase 2 study, 65 women with advanced platinum-resistant ovarian cancer were administered voreloxin at a dose of 48 mg/m2 as a single agent once every three weeks. At this dose, two patients have had a complete response, five have had partial responses and 23 achieved stable disease for 90 days or more. This equates to an overall disease control rate of 46%. Thirty-five women in the Phase 2 study were given 60 mg/m2 once every four weeks. Of the 32 patients evaluable for efficacy at this dose, one patient has had a complete response, two have had partial responses and 20 achieved stable disease thus far.

Voreloxin was also generally well tolerated in platinum-resistant ovarian cancer patients. Grade 3/4 non-hematologic adverse events (greater than or equal to 5%) at the 48 mg/m2 dose were low: fatigue (14%), vomiting (6%) and infections (8%). Low rates of febrile neutropenia occurred in 8% of the 65 patients evaluable for safety at 48 mg/m2 dosed every three weeks and 6% of the 35 patients evaluable for safety at 60 mg/m2 dosed every four weeks. Based on this emerging safety profile and low incidence of febrile neutropenia, the dose of voreloxin has been escalated to 75 mg/m2 dosed every four weeks. Sunesis expects to complete enrollment of the 75 mg/m2 cohort by the end of 2008.

Voreloxin (formerly SNS-595), is a novel naphthyridine analog, structurally related to quinolones, a class of compounds that has not been used previously for the treatment of cancer. Voreloxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site- selective DNA damage, irreversible G2 arrest and apoptosis. Voreloxin is currently being evaluated in a Phase 2 clinical trial (known as the REVEAL-1 trial) in previously untreated elderly AML patients and in a Phase 1b/2 clinical trial combining voreloxin with cytarabine for the treatment of patients with relapsed/refractory AML, as well as in an ongoing Phase 2 single-agent trial in platinum-resistant ovarian cancer. In clinical trials conducted to date, voreloxin has been generally well tolerated and has shown objective responses in both solid and hematologic tumor types.