Æterna Zentaris Partner Keryx Announces Special Protocol Assessment Agreement with FDA for Phase 3 Trial of Perifosine (KRX-0401) in the Treatment of Patients with Refractory Metastatic Colorectal Cancer
Phase 3 X-PECT Trial (Xeloda(R) + Perifosine Evaluation in Colorectal cancer Treatment) to be led by Dr. Johanna Bendell, Director, GI Oncology Research, Sarah Cannon Research Institute
QUÉBEC CITY, Feb. 3 /PRNewswire-FirstCall/ - Æterna Zentaris Inc. (Nasdaq: AEZS; TSX: AEZ) (the "Company"), a late-stage drug development company specialized in oncology and endocrinology, today announced that its partner, Keryx Biopharmaceuticals (Nasdaq: KERX), has reached an agreement with the U.S. Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design of a Phase 3 trial for its PI3K/Akt pathway inhibitor, perifosine (KRX-0401), in patients with refractory metastatic colorectal cancer. The SPA provides agreement that the Phase 3 study design adequately addresses objectives in support of a regulatory submission. Keryx is Æterna Zentaris' partner and licensee for perifosine in the United States, Canada and Mexico. Perifosine is also out-licensed to Handok in South Korea while Æterna Zentaris retains rights for the rest of the world.
About the Phase 3 Trial Design
The Phase 3 X-PECT (Xeloda(R) + Perifosine Evaluation in Colorectal cancer Treatment) trial will be a randomized (1:1), double-blind trial comparing the efficacy and safety of perifosine + capecitabine (capecitabine is a chemotherapy marketed by Roche as Xeloda(R)) vs. placebo + capecitabine in approximately 430 patients with refractory metastatic colorectal cancer. Patients must have failed available therapy including 5-fluorouracil (5-FU), oxaliplatin (Eloxatin(R)), irinotecan, bevacizumab (Avastin(R)) and, if K-Ras wild-type (WT), failed therapy with prior cetuximab (Erbitux(R)) or panitumumab (Vectibix(R)). For oxaliplatin-based therapy, failure of therapy will also include patients who discontinued due to toxicity. The primary endpoint is overall survival (OS), with secondary endpoints including overall response rate (ORR: complete responses + partial responses), progression-free survival (PFS) and safety. The median OS for the X-PECT study's targeted patient population which has failed prior therapies as described above, is approximately 5 months. The X-PECT study will be powered at 90% to detect a statistically significant difference in OS, with an assumed median OS for the control arm of 5-6 months and 7-8 months for the perifosine arm. Approximately 360 events of death will trigger the un-blinding of the study.
Approximately 40 to 50 U.S. sites will participate in the study. The study is expected to begin in 2Q 2010, and enrollment is expected to take approximately 12 months, with study completion expected in 2H 2011. Dr. Johanna Bendell, Director of GI Oncology Research for the Sarah Cannon Research Institute, Nashville, Tennessee, will lead the Phase 3 investigational team that includes Dr. Cathy Eng, Associate Medical Director for the Colorectal Center at MD Anderson Cancer Center in Houston, Texas.
Dr. Johanna Bendell, commented, "More active agents are needed to improve survival for patients with metastatic colorectal cancer. We are very excited about this Phase 3 trial, which is based on the encouraging randomized Phase 2 data that demonstrated an improvement in overall survival and time to progression using perifosine plus capecitabine over placebo plus capecitabine in patients with metastatic colorectal cancer. As such, we are moving forward with the randomized Phase 3 X-PECT trial, and we hope to continue to see these improvements in patient outcomes."
Juergen Engel, Ph.D., President and CEO at Æterna Zentaris stated, "We are very excited about this significant milestone and would like to reiterate our thanks to our partner Keryx and the investigators for their valuable collaboration in the development of perifosine. In 2010, this novel oral anticancer compound will now be the subject of two Phase 3 registration trials, and we look forward to its further late-stage development in other indications in oncology in the coming future."
About Colorectal Cancer
According to the American Cancer Society, colorectal cancer is the third most common form of cancer diagnosed in the United States. It is estimated that over 146,000 people were diagnosed with some form of colorectal cancer with over 49,000 patients dying from colorectal cancer in 2009. Surgery is often the main treatment for early stage colorectal cancer. When colorectal cancer metastasizes (spreads to other parts of the body such as the liver) chemotherapy is commonly used. Treatment of patients with recurrent or advanced colorectal cancer depends on the location of the disease. Chemotherapy regimens (i.e. FOLFOX or FOLFIRI either with or without bevacizumab) have been shown to increase survival rates in patients with metastatic/advanced colorectal cancer. Currently, there are seven approved drugs for patients with metastatic colorectal cancer: 5-fluorouracil (5-FU), capecitabine (Xeloda(R)), irinotecan (Camptosar(R)), oxaliplatin (Eloxatin(R)), bevacizumab (Avastin(R)), cetuximab (Erbitux(R)), and panitumumab (Vectibix(R)). Depending on the stage of the cancer, two or more of these types of treatment may be combined at the same time or used after one another. For example, FOLFOX combines 5-FU, leucovorin and oxaliplatin and FOLFIRI combines 5-FU, leucovorin and irinotecan. Bevacizumab, a VEGF monoclonal antibody, is commonly administered with chemotherapy. Typically, patients who fail 5-FU, oxaliplatin, irinotecan, and bevacizumab-containing therapies, and who have wild-type KRAS status receive EGFR monoclonal antibody therapy with either cetuximab or panitumumab. Once patients progress on these agents, there are no further standard treatment options.
About Perifosine (KRX-0401)
Perifosine is a novel 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 both safety and clinical efficacy in several tumor types, both as a single agent and in combination with novel therapies. Perifosine is currently in a Phase 3 trial, under Special Protocol Assessment (SPA), in multiple myeloma for which it has received Orphan Drug and Fast Track designations from the FDA in this indication. Perifosine is also in Phase 2 clinical trials for several other tumor types.
About Special Protocol Assessments
The Special Protocol Assessment (SPA) process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a new drug application.
Final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the Phase 3 trial. The SPA agreement may only be changed through a written agreement between the sponsor and the FDA, or if the FDA becomes aware of a substantial scientific issue essential to product efficacy or safety. For more information on the Special Protocol Assessment process, please visit: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080571.pdf.
About Æterna Zentaris Inc.
Æterna Zentaris Inc. is a late-stage drug development company specialized in oncology and endocrinology. News releases and additional information are available at www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of the Company to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned not to rely on these forward-looking statements. The Company does not undertake to update these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments except if we are required by a governmental authority or applicable law.
SOURCE AETERNA ZENTARIS INC.
Share this article