CAMBRIDGE, Mass, Dec. 5 /PRNewswire-FirstCall/ -- Genzyme Corp. (Nasdaq: GENZ) announced today that the company has completed enrollment of 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. Data from this study are expected to provide substantial evidence for expanding the current product label into adult AML.
"We are very pleased to have reached this milestone and to have done so in a timeframe that we expect will allow us to present preliminary data at ASCO next spring," stated Mark Enyedy, president of Genzyme Oncology. "The completion of patient enrollment in this clinical study is another important step in our plan to broaden the Clolar label to benefit a larger patient population and address multiple lines of adult AML."
Genzyme has held preliminary discussions with the U.S. Food and Drug Administration in advance of submitting a supplemental new drug application (sNDA) for clofarabine as an initial treatment in older adults with AML. The company expects to file this sNDA in the second half of next year.
Significant Unmet Medical Need
The clinical trial, known as CLASSIC II, 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. Older AML patients often have disease features such as unfavorable cytogenetics and prior blood disorders that result in lower response rates and poorer outcomes to standard induction chemotherapy. In addition, standard therapy is poorly tolerated in older patients and early induction mortality exceeds 30 percent in patients with poor risk factors.
This study 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.
The CLASSIC II trial was designed to enroll 109 patients at 20 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 disorder such as myelodysplastic syndromes (MDS), poor health performance, or intermediate or unfavorable cytogenetics.
The primary endpoint is overall remission rate measured as either complete remission or complete remission with incomplete platelet recovery. Secondary endpoints include duration of remission, disease free survival, overall survival, safety and thirty-day mortality rate.
Patients receive an induction cycle of intravenous clofarabine administered as 30mg/m2 per day for five consecutive days then, based on response, receive up to five additional cycles of treatment at a dose of 20 mg/m2 per day for five consecutive days. The first stage of the CLASSIC II trial required at least 11 responses in the first 59 patients to continue to the second stage of the study. In September, Genzyme announced that the number of responding patients had exceeded this requirement.
Clolar Clinical Development
A separate, phase 3 pivotal study (CLASSIC I) of clofarabine in adult AML patients aged 55 and older and previously treated with at least one, but not more than two, prior induction regimens is underway. It is a randomized, double-blind, controlled study that will compare the combination of clofarabine 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 compare clofarabine to standard therapy in 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.
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.
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. Since 1981, the company has grown from a small start-up to a diversified enterprise with more than 9,500 employees in locations spanning the globe and 2006 revenues of $3.2 billion. In 2007, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation. In 2006 and 2007, Genzyme was 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 nearly 90 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 diagnostic testing. Genzyme's commitment to innovation continues today with a substantial development program focused on these fields, as well as immune disease, infectious 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 expected results of the data generated from the Clolar clinical 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; the timing and content of decisions by the FDA related to clinical trials and approval of Clolar in additional indications; the actual efficacy and safety of Clolar for the indications in which it is being tested; and the risks and uncertainties described in reports filed by Genzyme with the U.S. Securities and Exchange Commission, including without limitation the factors discussed under the caption "Risk Factors" in Genzyme's Quarterly Report on Form 10-Q for the quarter ended September 30, 2007. We caution investors not to place undue reliance on the forward-looking statements contained in this press release. These statements speak only as of the date of this press release, and we undertake no obligation to update or revise the statements.
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|SOURCE Genzyme Corp.|
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