FDA Approves Chemotherapeutic Enzyme L-Asparaginase

The Food and Drug Administration on Nov. 18 granted orphan drug status to asparaginase Erwinia chrysanthemi, a chemotherapeutic enzyme indicated for patients with acute lymphoblastic leukemia* who have become allergic to pegaspargase or asparaginase derived from Escherichia coli.

The new drug (Erwinaze) is derived from Erwinia chrysanthemi, a gram-negative bacillus related to E. coli.

It works by the same mechanism as the two previously approved agents – blocking asparagine, a protein necessary for the proliferation of neoplastic cells, according to an FDA press statement.

"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 end points," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

According to the prescribing information, asparaginase Erwinia chrysanthemi is indicated as part of a multi-agent treatment regimen for patients with hypersensitivity to E. coli–derived asparaginase.

To substitute for a dose of pegaspargase, patients should receive 25,000 IU/m² of asparaginase Erwinia chrysanthemi administered intramuscularly three times a week (six doses for each planned dose of pegaspargase). To substitute for a dose of native E. coli asparaginase, the recommended dose of asparaginase Erwinia chrysanthemi is 25,000 IU/m² intramuscularly for each scheduled dose of the E. coli–derived drug.

Two pivotal trials influenced the approval, the press statement noted. These included the ongoing Erwinase Master Treatment Protocol with full data on 843 patients, and a completed trial of 58 patients.

In each study, the main end point was the number of patients with sustained asparaginase activity levels that have been correlated with better disease control and survival, according to a statement on the National Cancer Institute Web site.

"The major efficacy outcome was attainment of sustained serum asparaginase activity levels of 0.1 IU/mL or higher, which has been demonstrated to correlate with asparagine depletion and to serum levels that predict clinical efficacy," according to the prescribing information. Among 48 patients with available samples, all achieved this threshold trough level of asparaginase activity.

The most common side effect associated with the drug was allergic reaction (17%), the prescribing information notes. Other side effects included pancreatitis (4%), coagulation abnormalities (3%), abnormal liver function (4%), and hyperglycemia (2%).

Nausea, vomiting, or abdominal pain was reported in 5%, while headache, diarrhea, or seizure occurred in 1% each.

EUSA Pharma Inc. of Langhorne, Pa., manufactures the drug. A patient education page is available.

*CORRECTION 12/22/11: This sentence originally stated that the enzyme was indicated for chronic lymphoblastic anemia. The sentence has been corrected to chronic lymphoblastic leukemia.

The Food and Drug Administration on Nov. 18 granted orphan drug status to asparaginase Erwinia chrysanthemi, a chemotherapeutic enzyme indicated for patients with acute lymphoblastic leukemia* who have become allergic to pegaspargase or asparaginase derived from Escherichia coli.

The new drug (Erwinaze) is derived from Erwinia chrysanthemi, a gram-negative bacillus related to E. coli.

It works by the same mechanism as the two previously approved agents – blocking asparagine, a protein necessary for the proliferation of neoplastic cells, according to an FDA press statement.

"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 end points," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

According to the prescribing information, asparaginase Erwinia chrysanthemi is indicated as part of a multi-agent treatment regimen for patients with hypersensitivity to E. coli–derived asparaginase.

To substitute for a dose of pegaspargase, patients should receive 25,000 IU/m² of asparaginase Erwinia chrysanthemi administered intramuscularly three times a week (six doses for each planned dose of pegaspargase). To substitute for a dose of native E. coli asparaginase, the recommended dose of asparaginase Erwinia chrysanthemi is 25,000 IU/m² intramuscularly for each scheduled dose of the E. coli–derived drug.

Two pivotal trials influenced the approval, the press statement noted. These included the ongoing Erwinase Master Treatment Protocol with full data on 843 patients, and a completed trial of 58 patients.

In each study, the main end point was the number of patients with sustained asparaginase activity levels that have been correlated with better disease control and survival, according to a statement on the National Cancer Institute Web site.

"The major efficacy outcome was attainment of sustained serum asparaginase activity levels of 0.1 IU/mL or higher, which has been demonstrated to correlate with asparagine depletion and to serum levels that predict clinical efficacy," according to the prescribing information. Among 48 patients with available samples, all achieved this threshold trough level of asparaginase activity.

The most common side effect associated with the drug was allergic reaction (17%), the prescribing information notes. Other side effects included pancreatitis (4%), coagulation abnormalities (3%), abnormal liver function (4%), and hyperglycemia (2%).

Nausea, vomiting, or abdominal pain was reported in 5%, while headache, diarrhea, or seizure occurred in 1% each.

EUSA Pharma Inc. of Langhorne, Pa., manufactures the drug. A patient education page is available.

*CORRECTION 12/22/11: This sentence originally stated that the enzyme was indicated for chronic lymphoblastic anemia. The sentence has been corrected to chronic lymphoblastic leukemia.

The Food and Drug Administration on Nov. 18 granted orphan drug status to asparaginase Erwinia chrysanthemi, a chemotherapeutic enzyme indicated for patients with acute lymphoblastic leukemia* who have become allergic to pegaspargase or asparaginase derived from Escherichia coli.

The new drug (Erwinaze) is derived from Erwinia chrysanthemi, a gram-negative bacillus related to E. coli.

It works by the same mechanism as the two previously approved agents – blocking asparagine, a protein necessary for the proliferation of neoplastic cells, according to an FDA press statement.

"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 end points," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

According to the prescribing information, asparaginase Erwinia chrysanthemi is indicated as part of a multi-agent treatment regimen for patients with hypersensitivity to E. coli–derived asparaginase.

To substitute for a dose of pegaspargase, patients should receive 25,000 IU/m² of asparaginase Erwinia chrysanthemi administered intramuscularly three times a week (six doses for each planned dose of pegaspargase). To substitute for a dose of native E. coli asparaginase, the recommended dose of asparaginase Erwinia chrysanthemi is 25,000 IU/m² intramuscularly for each scheduled dose of the E. coli–derived drug.

Two pivotal trials influenced the approval, the press statement noted. These included the ongoing Erwinase Master Treatment Protocol with full data on 843 patients, and a completed trial of 58 patients.

In each study, the main end point was the number of patients with sustained asparaginase activity levels that have been correlated with better disease control and survival, according to a statement on the National Cancer Institute Web site.

"The major efficacy outcome was attainment of sustained serum asparaginase activity levels of 0.1 IU/mL or higher, which has been demonstrated to correlate with asparagine depletion and to serum levels that predict clinical efficacy," according to the prescribing information. Among 48 patients with available samples, all achieved this threshold trough level of asparaginase activity.

The most common side effect associated with the drug was allergic reaction (17%), the prescribing information notes. Other side effects included pancreatitis (4%), coagulation abnormalities (3%), abnormal liver function (4%), and hyperglycemia (2%).

Nausea, vomiting, or abdominal pain was reported in 5%, while headache, diarrhea, or seizure occurred in 1% each.

EUSA Pharma Inc. of Langhorne, Pa., manufactures the drug. A patient education page is available.

*CORRECTION 12/22/11: This sentence originally stated that the enzyme was indicated for chronic lymphoblastic anemia. The sentence has been corrected to chronic lymphoblastic leukemia.