CAMBRIDGE, Mass., Dec. 29 /PRNewswire-FirstCall/ -- Genzyme Corp. announced today that the U.S. Food and Drug Administration (FDA) has granted marketing approval for CLOLAR(TM) (clofarabine) for the treatment of children with refractory or relapsed acute lymphoblastic leukemia (ALL). CLOLAR is the first new leukemia treatment approved specifically for children in more than a decade. Given the unmet need for new treatment options in this seriously ill patient population, Genzyme expects to make CLOLAR commercially available as quickly as possible in January.
"FDA approval of CLOLAR is a welcome sign that industry and the agency are beginning to act on the needs of children with cancer very early in oncology drug development," said Susan Weiner, Ph.D., president of The Children's Cause for Cancer Advocacy. "Children resistant to current treatments badly need new therapeutic options, and hopefully this approval will encourage others in industry to meet the unmet medical needs of these very sick children."
In 2005, an estimated 3,400 new cases of pediatric acute leukemia will be diagnosed in the United States, according to Cancer Metric. ALL is the most common form of pediatric leukemia and children who do not respond to initial therapy, or who relapse, have a very poor survival prognosis.
"We are very pleased that the FDA has moved so assertively in making children suffering from cancer a priority in new drug development," said Duke Collier, executive vice president, Genzyme Corporation. "We are excited to offer these young patients and their physicians new hope through CLOLAR."
CLOLAR(TM) 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.
CLOLAR has received Orphan Drug designation for adult and pediatric acute lymphoblastic leukemia. CLOLAR will now have seven years of market exclusivity in pediatric ALL patients. The FDA also recently granted six months of extended market exclusivity to CLOLAR under the Best Pharmaceuticals for Children Act.
CLOLAR was approved under the FDA's accelerated approval process, which was established for serious or life-threatening diseases such as ALL where a product may provide meaningful therapeutic benefit to patients over existing treatments. Approvals can be granted on the basis of adequate and well- controlled clinical trials establishing that the product has an effect on a surrogate endpoint reasonably likely to predict clinical benefit. Post- marketing studies to verify clinical benefit are required under this mechanism. Genzyme is committed to continue post-marketing evaluation of CLOLAR in pediatric ALL and has submitted a pediatric development plan that includes further study of CLOLAR in combination with existing therapies.
"With this approval, we will now expand our commercial operations, including the creation of Genzyme's first oncology sales force for CLOLAR," stated Mark Enyedy, senior vice president and general manager of Genzyme Oncology. "We have worked diligently to make CLOLAR available to physicians and patients, and are eager to embark on the product launch. This is the first step in our comprehensive development plan for CLOLAR, which we are also studying for adult leukemia and solid tumor cancers."
Clinical Trial Results
CLOLAR's approval was based on results from a pivotal Phase II trial involving 49 heavily pretreated children with relapsed or refractory ALL. Patients received 52mg/m2 of CLOLAR intravenously for one to two hours a day for five consecutive days. This process was repeated for two to six cycles every 28 days depending on response to treatment and blood count recovery.
In the study, a 30 percent response rate was achieved, with 20 percent of all patients achieving a complete remission (CR) or a complete marrow remission in the absence of platelet recovery (CRp) and 10 percent of all patients achieving a partial response (PR). Seven patients (14 percent) went on to receive bone marrow or stem cell transplants following treatment with CLOLAR.
Results of 12 additional patients were recently presented at the American Society of Hematology 46th Annual Meeting and Exposition in San Diego and supported a 30 percent response rate in this same patient population.
"The children who participated in the CLOLAR study had failed an average of three prior treatment regimens and had very poor chances of survival," said lead CLOLAR investigator Sima Jeha, MD, director, Developmental Therapeutics, Division of Leukemia/Lymphoma, St. Jude Children's Research Hospital. "As a pediatric oncologist, I am excited to have a new well-tolerated and effective treatment option for these patients with highly-resistant leukemia."
CLOLAR has also been studied in children with relapsed or refractory acute myeloid leukemia (AML). A Phase II study to date has shown a 26 percent response rate in 42 children with this leukemia, with one CRp and 10 partial remissions (PR). In addition, 34 percent, or 12 patients, treated with clofarabine went to transplant. On December 1, 2004, the Oncologic Drugs Advisory Committee of the FDA advised conducting additional studies in this group before recommending an AML approval. Plans are currently underway to further support CLOLAR in this setting.
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 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. Assessment of respiratory status and blood pressure monitoring during infusion with CLOLAR is recommended. CLOLAR should be discontinued immediately in the event of clinically significant signs or symptoms of SIRS or capillary leak syndrome and appropriate supportive care measures initiated. The most common adverse effects after CLOLAR treatment, regardless of causality, were gastrointestinal tract symptoms, including vomiting, nausea, and diarrhea; hematologic effects, including anemia, leucopenia, thrombocytopenia, neutropenia, and febrile neutropenia; and infection. Careful hematologic monitoring during therapy is important.
Hepatic and renal function should be assessed prior to and during treatment with CLOLAR, as the liver is a target organ for CLOLAR toxicity and the kidneys are the predominant mode of CLOLAR excretion. Cardiac disorders included tachycardia, pericardial effusion, and left ventricular systolic dysfunction in up to 35% of patients. 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 http://www.clolar.com/.
Genzyme Corporation is a global biotechnology company dedicated to making a major positive impact on the lives of people with serious diseases. The company's broad product portfolio is focused on rare genetic disorders, renal disease, osteoarthritis, cancer and immune-mediated diseases, and includes an industry-leading array of diagnostic products and services and sophisticated biomaterials. Genzyme's commitment to innovation continues today with expanded research into novel approaches to treat cancer, heart disease, and other areas of unmet medical need. More than 7,000 Genzyme employees in offices around the globe serve patients in over 80 countries.
This press release contains forward-looking statements, including statements about: the timing of the commercial availability of CLOLAR; the number of patients diagnosed with pediatric leukemia; the expansion of commercial operations in support of CLOLAR, and plans to conduct additional clinical studies with CLOLAR. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties include, among others: the ability of Genzyme's contract manufacturer and logistics agent to make CLOLAR commercially available in the time predicted; the accuracy of third party estimates of the number of pediatric oncology patients; Genzyme's ability to recruit and hire qualified sales, marketing, and other personnel in support of CLOLAR; actual timing and content of submissions to and decisions made by the FDA and institutional review boards of entities conducting clinical trials for CLOLAR, as well as the ability to recruit patients to participate in these trials; and the risks and uncertainties described in reports filed by Genzyme with the Securities and Exchange Commission. Please see the disclosure 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 quarter ended September 30, 2004 for a more complete discussion of these and other risks. 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 the statements.
CLOLAR(TM) is a trademark of ILEX Products, Inc., a subsidiary of Genzyme Corporation. All rights reserved.
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