QUEBEC CITY, Canada, June 5 /PRNewswire-FirstCall/ - AEterna Zentaris’ North American partner Keryx Biopharmaceuticals disclosed positive data of perifosine (KRX-0401) in patients with advanced renal cell carcinoma (RCC). These patients were a cohort of a phase 2, multi- center, trial of perifosine that included multiple tumor types. All patients in this study were to have had prior standard therapy. Although the extent of prior treatment varied with tumor type, most patients had received two chemotherapy regimens for metastatic disease. An interim analysis was performed at the end of the first year of accrual, and the results in the renal group met protocol requirements for expansion of this cohort. The study is ongoing.
Thirteen patients with advanced renal cell carcinoma (RCC) were enrolled in the study and 7 were evaluable for response. Three of these (43%) had a partial response and an additional 2 patients (29%) achieved long-term stable disease. Two progressed. Four patients were inevaluable because they stopped treatment early (42 -62 days) and their disease was not evaluated at the time drug was stopped. Two patients have not been on study long enough to reach the first point of evaluation. Responses were scored using RECIST criteria.
<< Response N (%) Duration (months) Partial Response 3 (43%) 4, 4+, 9 Stable Disease 2 (29%) 8+, 11 Progression 2 (29%) 2, 3 Too Early 2 Not Evaluable 4 >> Times with '+' meaning patient still stable or responding at time of analysis.
Additional renal patients will be enrolled on this study, including patients with prior exposure to sorafenib and sunitinib. Keryx anticipates that phase 1 studies combining perifosine with approved agents for the treatment of renal cell cancer will be opened within 6-8 weeks. Larger and more definitive phase 2 and phase 3 trials are being developed, and it is anticipated that one or more of these will be initiated in the next 6 - 12 months.
“The Akt pathway is frequently activated in renal cell cancers. It follows that this tumor type may be particularly responsive to Akt inhibition, and we think these studies with perifosine may be providing early evidence of this”, said I. Craig Henderson, M.D., President of Keryx Biopharmaceuticals. Henderson also added, “Therapy with perifosine could potentially provide an important advancement in the treatment of renal cell carcinoma, a disease that affects 39,000 new patients every year in the US.”
“Recent approvals of sorafenib and sunitinib provide great hope for patients with renal cell carcinoma. However, additional treatments are desperately needed, particularly agents with a different mechanism of action”, stated Robert Figlin, MD, professor of medicine and urology, David Geffen School of Medicine at UCLA. “This response data is preliminary but of great interest and we are anxious to further explore the potential of perifosine, a novel agent that targets Akt and other important pathways known to cause resistance in renal cell carcinoma.”
Dr. Jurgen Engel, Executive Vice President, Global R&D and Chief Operating Officer at AEterna Zentaris concluded, “I believe this data is proof of perifosine’s anticancer activity as a monotherapy agent in this specific indication, which may open other multiple opportunities.”
About the Phase 2 Trial Design
This Keryx-sponsored, exploratory trial was designed to evaluate the safety and efficacy of two schedules of perifosine (KRX-0401) in patients with a variety of tumor types. From February 2005 to February 2006, patients at over 30 centers across the US were randomized to receive either 50 mg of perifosine once daily or 1200 mg on a weekly dose schedule. The protocol was designed to accrue 11 patients in a given tumor type and then expand that cohort to 26 patients if a favorable outcome is seen in at least 1 of the first 11 patients. The study continues to enroll patients, and no cohort defined by tumor type has been closed because of insufficient evidence of activity. The responses we have seen in this advanced renal cell carcinoma cohort did not appear dose-dependent as partial responses and stable disease were noted in both dose groups. This is consistent with prior data with perifosine where responses have been equally distributed between higher and lower dose groups.
Toxicity
The 50 mg dose has been extremely well tolerated. The main toxicities were nausea, vomiting, diarrhea, and fatigue. Nearly half (42%) of the patients on this dose had none of these symptoms, and 89% had no gastrointestinal toxicity above grade 1. The incidence of grade 2 or greater toxicity with the weekly dose was considerably higher, but even in this group nearly 20% experienced none of these side effects and one third no gastrointestinal toxicity above grade 1. The frequency of grade 2 or higher toxicity by study arm was:
<< Adverse Event 50 mg Daily Arm 1200 mg Weekly Arm N (equal sign) 90 N (equal sign) 95 Nausea 5 (6%) 30 (32%) Vomiting 4 (5%) 19 (20%) Diarrhea 5 (6%) 34 (36%) Fatigue 13 (14%) 27 (28%) >> About Renal Cell Carcinoma
RCC represents approximately 2% to 3% of all adult cancers worldwide and 2% of all cancer-related deaths. In 2006, an estimated 39,000 new cases of RCC and 13,000 deaths attributable to RCC are expected in the US. The National Cancer Institute reports a rising incidence of RCC at a rate of approximately 2% per decade. The disease occurs predominantly in the seventh and eighth decades in life, and it affects nearly twice as many men as women.
About Perifosine (KRX-0401)
Perifosine is a novel, first-in-class, oral anticancer agent that modulates several key signal transduction pathways, including AKT, MAPK, and JNK that have been shown to be critical for the survival of cancer cells. Perifosine has demonstrated single agent anti-tumor activity in Phase I and Phase II studies and is currently being studied as a single agent and in combination with several forms of anti-cancer treatments for various forms of cancer, including non-small cell lung cancer and breast cancer.
About AEterna Zentaris Inc.
AEterna Zentaris Inc. is a growing global biopharmaceutical company engaged in the discovery, development and marketing of therapies for cancer and endocrine disorders. AEterna Zentaris also owns 48.29% of the equity of Atrium Biotechnologies Inc. and 64.7% of its voting rights. Atrium is a developer, manufacturer and marketer of science-based products for the cosmetics, pharmaceutical, chemical and nutritional industries.
News releases and additional information are available at www.aeternazentaris.com.
Forward-Looking Statements
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AETERNA ZENTARIS INC. (FORMERLY/ANCIENNEMENT - LES LABORATOIRES AETERNA
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