Genzyme Begins Phase 3 Pivotal Study of Clolar® in Adult Acute Myelogenous Leukemia
September 6, 2006 - Genzyme Corporation (Nasdaq: GENZ) announced today that the first patient has been treated in a new phase 3 clinical trial examining the safety and effectiveness of Clolar® (clofarabine) in older patients with acute myelogenous leukemia (AML). This is the first pivotal clinical study of clofarabine in adult patients with AML, and is expected to provide substantial support for expanding the current product label.
“We are very pleased to initiate 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 an important next step in our plan to broaden Clolar’s label to benefit a larger patient population and address multiple lines of adult AML.”
Phase 3 Design and Focus on Adult AML
The trial, designed as a pivotal study for adult AML patients aged 60 and older previously treated with at least one, but not more than two prior induction regimens, is a randomized, double-blind, controlled study that will compare the combination of Clolar and cytarabine (Ara-C) to cytarabine alone. The study will take place at approximately 100 medical centers in the United States and Canada. It will enroll up to 376 patients with refractory or relapsed AML.
“There is significant unmet medical need in relapsed, refractory adult AML and clofarabine could represent an important therapeutic option for these older patients,” stated Stefan Faderl, M.D., The University of Texas M. D. Anderson Cancer Center and principal investigator of the study. “This clinical trial is a natural and important extension of M. D. Anderson’s experience with the clofarabine and cytarabine combination. It will help us to further determine the position of clofarabine combinations in the management of adult patients with AML.”
In addition to safety, the trial will evaluate the effectiveness of one dose of 40 mg/m² per day of Clolar combined with 1 g/m² per day of Ara-C, compared with 1g/m2 per day of Ara-C combined with placebo. The primary endpoint is improved overall survival. Other endpoints include overall remission rate, duration of remission, disease-free survival and event-free survival and safety and tolerability including hospitalizations. All patients will be followed for at least two years after their end of treatment visit.
A separate, phase 2 pivotal study of clofarabine in previously untreated older AML patients for whom standard induction combination chemotherapy is unlikely to be of benefit is expected to begin as early as the fourth quarter of this year. A second phase 3 study of clofarabine sponsored by the Eastern Cooperative Oncology Group is expected to begin enrolling patients early 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.
Ongoing Clinical Development
Genzyme successfully entered the oncology market in 2005 with the launch of Clolar, the first cancer treatment approved specifically for pediatric patients in more than a decade. As in adults, Genzyme is conducting parallel clinical studies in children. Clolar in combination with existing therapies is being studied in two phase 1/2 studies, one of which is underway. These studies are part of post-marketing commitments that Genzyme made to the FDA following the accelerated approval of Clolar.
The first phase 1/2 trial is evaluating Clolar in combination with the chemotherapy agents etoposide and cyclophosphamide in patients with no more than two (AML) or three (ALL) prior induction regimens. The primary objective of the phase 1 portion of the study is to define the maximum tolerated dose, dose-limiting toxicities, and recommended phase 2 dose of clofarabine in combination with these two agents. In the phase 2 portion of the study involving ALL patients only, the primary objective is to assess the efficacy of Clolar in combination with etoposide and cyclophosphamide, as determined by the complete remission, complete remission without platelet recovery, and overall remission rate. Thirty-nine patients are expected to be treated during the enrollment period.
The second phase 1/2 trial is sponsored by the Children’s Oncology Group. This trial is evaluating Clolar in combination with cytarabine. Its primary objective is to measure overall response rate in AML and ALL patients 30 years of age and younger who have recurrent disease or are refractory to induction therapy. Eighty-seven patients are expected to be enrolled in this study over the course of 24 months. Based upon the experience with these two studies, Genzyme will continue to consult with the U.S. Food and Drug Administration regarding the final appropriate design of a randomized phase 3 study to demonstrate clinical benefit in the pediatric population with ALL.
Genzyme seeks to explore additional therapeutic indications for Clolar through its support of several investigator initiated studies. Additionally, Genzyme is enrolling patients in its phase 1 trial of clofarabine in solid tumors and continues to consider development in myelodysplastic syndrome (MDS).
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. The most common side effects seen after Clolar treatment, regardless of causality, are vomiting, nausea, diarrhea, low blood counts, fever and infection. Careful monitoring of blood counts during therapy is important since Clolar can cause reversible and dose dependent suppression of bone marrow function, which may increase the risk of infection, including severe sepsis. Administration of Clolar results in a rapid reduction in peripheral leukemia cells. Patients should be evaluated and monitored for signs and symptoms of tumor lysis syndrome and cytokine release that could develop into systemic inflammatory response syndrome (SIRS)/capillary leak syndrome, and organ dysfunction.
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 primary through the kidneys. 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.
For more information about Clolar, please call 1-800-RX CLOLAR or visit www.CLOLAR.com.
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 June 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.
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.
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