Genzyme Initiates Clinical Trial Of Clofarabine In Adult AML

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Genzyme has completed enrollment of a phase 2 clinical trial examining the safety and effectiveness of Clolar (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.

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Study Design

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.

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