The FDA has approved asparaginase Erwinia chrysanthemi (Erwinaze) to treat patients with acute lymphoblastic leukemia who have developed hypersensitivity to Escherichia coli–derived asparaginase (Elspar) and pegaspargase (Oncaspar). Acute lymphoblastic leukemia is the most commonly diagnosed childhood cancer. An estimated 15% to 20% of patients develop hypersensitivity to products derived from E coli.
Asparaginase E chrysanthemi is injected directly into the muscle three times a week and works by depleting the level of asparagine in the blood. Asparagine is essential for cell growth, and its removal from the blood inhibits the growth of cells associated with acute lymphoblastic leukemia. Normal human cells are able to make enough asparagine for their own needs through biosynthesis and will not be affected by treatment with asparaginase E chrysanthemi.
“The approval of Erwinaze underscores the FDA’s commitment to the approval of drugs for conditions with limited patient populations with unmet medical needs using novel trial endpoints,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.
Key Clinical Trials
The safety and effectiveness of the new agent was evaluated in one clinical trial of 58 patients. Additional safety data were collected from the Erwinaze Master Treatment Protocol (EMTP), an expanded access program that enrolled 843 patients. Patients in both studies were unable to continue receiving pegaspargase or asparaginase derived from E coli due to allergic reactions.
In the trial to support efficacy, the endpoint was the measurement of the proportion of patients with sustained asparaginase activity levels that correlate with better leukemia control and survival. All evaluable patients were shown to have maintained the prespecified threshold for asparaginase activity at 48 or 72 hours after dosing.
Side effects associated with asparaginase E chrysanthemi treatment include serious hypersensitivity (including anaphylaxis), pancreatitis, abnormal transaminase and bilirubin levels, blood clotting, hemorrhage, nausea, vomiting, and hyperglycemia.
Asparaginase E chrysanthemi has been designated as an orphan drug, which identifies the disease as affecting fewer than 200,000 people in the United States. The drug is manufactured by EUSA Pharma Inc, Langhorne, Pennsylvania. ■