CAMBRIDGE, Mass., Nov. 27 /PRNewswire-FirstCall/ -- Genzyme Corporation announced today that it has begun treating patients in a phase 2 clinical trial examining the safety and effectiveness of Clolar(R) (clofarabine) in previously untreated, older adult patients with acute myelogenous leukemia (AML) who are unlikely to benefit from standard induction therapy. This is Genzyme’s second pivotal clinical study of clofarabine in adult patients with AML to commence this year, and it is expected to provide substantial support for expanding the current product label.
“We are very pleased to begin treatment in this clinical study as we seek to expand Clolar therapy to adult patients,” stated Mark Enyedy, senior vice- president and general manager of Genzyme Oncology. “Significant data from investigator-sponsored clinical trials have already been presented regarding the use of Clolar in adult AML and show very encouraging results. The start of this new clinical study is another important step in our plan to broaden Clolar’s label to benefit a larger patient population and address multiple lines of adult AML.”
The trial is designed to address a high unmet medical need among older AML patients who currently have limited treatment options. According to the American Cancer Society, each year approximately 6,500 people over the age of 60 are diagnosed with AML in the U.S. The median survival for those receiving therapy can vary from one to thirteen months, and the five-year survival rate over the past three decades remains at less than 15 percent. Standard therapy is poorly tolerated and early induction mortality exceeds 30 percent in patients with poor risk factors.
“While the outlook for children and young adults with AML has improved during the last three decades due to advances in chemotherapy and bone marrow transplant, the majority of AML patients are over the age of sixty years and not able to tolerate these curative approaches,” stated Harry Erba, M.D., Ph.D., of the University of Michigan Comprehensive Cancer Center. “This Genzyme-sponsored trial of clofarabine represents an attempt to develop a new effective therapy for this aggressive leukemia that can be tolerated by older patients.”
Hagop M. Kantarjian, M.D. of The University of Texas M. D. Anderson Cancer Center, added that complete remission and response rates remain low among older AML patients. “Standard therapies for AML in this population are unsatisfactory. Older patients are often faced with treatment choices at either end of the spectrum: either toxic combination chemotherapy that has a high chance of treatment-related morbidity and mortality despite a low chance of cure, or very shortened survival with supportive care alone.”
The clinical trial, known as CLASSIC II, builds on promising results from two phase 2 studies of clofarabine in previously untreated older patients with AML deemed unfit for chemotherapy. These studies were conducted by Alan Burnett, M.D., of Cardiff University in the United Kingdom. Dr. Burnett will present updated results from his UK clinical trials at the annual American Society of Hematology meeting taking place next month in Orlando, Florida.
Study Design
The CLASSIC II trial will enroll 109 patients at approximately 30 sites in the U.S. Patients must have AML, be 60 years or older and have at least one of the following adverse prognostic factors: age greater than or equal to 70, prior hematological disease such as myelodysplastic syndrome, poor health performance, or intermediate or unfavorable cytogenetics.
The primary endpoint is overall response measured as either complete response or complete response with incomplete platelet recovery. Secondary endpoints include duration of remission, disease free survival, overall survival, safety and thirty-day mortality rate.
Patients will receive an induction cycle of intravenous clofarabine administered as 30mg/m2 per day for five consecutive days, and based on response may receive up to five additional cycles of treatment at a dose of 20 mg/m2 per day for five consecutive days.
Clolar Clinical Development
A separate, phase 3 pivotal study (CLASSIC I) of clofarabine in adult AML patients aged 60 and older and previously treated with at least one, but not more than two, prior induction regimens began earlier this year. It is a randomized, double-blind, controlled study that will compare the combination of Clolar and cytarabine (Ara-C) to cytarabine alone.
A second phase 3 study of clofarabine sponsored by the Eastern Cooperative Oncology Group is expected to begin enrolling patients next year. This study will focus on untreated AML patients over the age of 60 who are considered suitable for standard induction chemotherapy.
Clolar is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory ALL after at least two prior regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.
Genzyme also is actively exploring additional therapeutic indications for Clolar, including in MDS.
About Clolar
Clolar has Orphan Drug designation for adult and pediatric ALL, and seven years of market exclusivity in the United States for relapsed/refractory pediatric ALL. The FDA also granted six months of extended market exclusivity to Clolar under the Best Pharmaceuticals for Children Act.
Clolar should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Suppression of bone marrow function, which is usually reversible and dose dependent, should be anticipated and is likely to increase the risk of infection, including severe sepsis. Administration of Clolar results in a rapid reduction of peripheral leukemia cells. Patients should be evaluated and monitored for signs and symptoms of tumor lysis syndrome and cytokine release (e.g., tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into systemic inflammatory response syndrome (SIRS)/capillary leak syndrome, and organ dysfunction. Clolar should be discontinued immediately in the event of clinically significant signs or symptoms of SIRS or capillary leak syndrome.
The most common side effects seen after Clolar treatment, regardless of causality, were gastrointestinal tract symptoms, including vomiting, nausea, and diarrhea; hematologic effects including anemia, leukopenia, thrombocytopenia, neutropenia, and febrile neutropenia; and infection.
Liver and kidney function should be assessed prior to and during treatment with Clolar, as the liver is a target organ for Clolar toxicity and Clolar is excreted primarily through the kidneys. Concomitant use of medications known to induce hepatic toxicity should be avoided. Cardiac disorders, including tachycardia, pericardial effusion, and left ventricular systolic dysfunction, have been noted in up to 35% of pediatric patients treated with Clolar. However, the presence of these disorders in patients prior to Clolar administration and/or previous therapy or concurrent illness in patients receiving Clolar makes the etiology of these disorders unclear.
Clolar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant and avoid breast feeding while receiving treatment with Clolar.
For more information about Clolar, please call 1-800-RX CLOLAR or visit http://www.CLOLAR.com.
About Genzyme
One of the world’s leading biotechnology companies, Genzyme is dedicated to making a major positive impact on the lives of people with serious diseases. This year marks the 25th anniversary of Genzyme’s founding. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 8,500 employees in locations spanning the globe and 2005 revenues of $2.7 billion. Genzyme has been selected by FORTUNE as one of the “100 Best Companies to Work for” in the United States. With many established products and services helping patients in more than 80 countries, Genzyme is a leader in the effort to develop and apply the most advanced technologies in the life sciences. The company’s products and services are focused on rare inherited disorders, kidney disease, orthopaedics, cancer, transplant and immune diseases, and diagnostic testing. Genzyme’s commitment to innovation continues today with a substantial development program focused on these fields, as well as heart disease and other areas of unmet medical need.
This press release contains forward-looking statements, including statements regarding the potential administration, dosing and therapeutic benefit of Clolar in various cancer indications; the planned timetable and enrollment for clinical trials of Clolar and the sites of such trials; and the requirements and plans for regulatory filings and approvals for Clolar in additional indications. These risks and uncertainties include, among others: the timing of discussions with the FDA regarding clinical studies and approval of Clolar in additional indications; Genzyme’s ability to engage cooperative groups to conduct clinical trials of Clolar and the ability of all clinical trial sites to enroll patients in the applicable study; the timing and content of decisions by institutional review boards and the FDA related to clinical trials and approval of Clolar in additional indications; and the actual efficacy and safety of Clolar for the indications in which it is being tested. Please refer to the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission under the heading “Factors Affecting Future Operating Results” in the Management’s Discussion and Analysis of Financial Condition and Results of Operations section of Genzyme’s Quarterly Report on Form 10-Q for the period ended September 30, 2006 for a more complete discussion of the risks associated with Genzyme’s business. Genzyme cautions investors not to place substantial reliance on the forward- looking statements contained in this press release. These statements speak only as of the date of this press release, and Genzyme undertakes no obligation to update or revise these statements.
Genzyme(R) and Clolar(R) are registered trademarks of Genzyme Corporation. All rights reserved.
Genzyme’s press releases and other company information are available at http://www.genzyme.com and by calling Genzyme’s investor information line at 1-800-905-4369 within the United States or 1-703-797-1866 outside the United States.
Media Contact: Investor Contact: Maria Cantor Carol Miceli (617) 768-6690 (617) 768-6602
Genzyme Corporation
CONTACT: Media Contact: Maria Cantor, +1-617-768-6690, or InvestorContact: Carol Miceli, +1-617-768-6602, both of Genzyme Corporation
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