"The U.S. Food and Drug Administration today expanded the approved use of Imbruvica (ibrutinib) for chronic lymphocytic leukemia (CLL) patients who have received at least one previous therapy.
CLL is a rare blood and bone marrow disease"...
Mechanism Of Action
Asparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine. The mechanism of action of ERWINAZE is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of amino acid asparagine for their protein metabolism and survival.
The pharmacokinetics of ERWINAZE has not been characterized. The serum trough concentrations of asparaginase Erwinia chrysanthemi were determined in 48 ALL patients aged ≥ 2 year to ≤ 18 years enrolled in Study 1 [see Clinical Studies]. Following administration of ERWINAZE 25,000 International Units/m² intramuscularly on a Monday, Wednesday, and Friday schedule for 6 doses, 100% of patients in course 1 achieved serum trough asparaginase concentrations ≥ 0.1 International Units/mL at either 48-hour (n=35) or 72-hour (n=13) post dose 3. Eighty percent (28/35) of those evaluated at 48 hours and 38% (5/13) evaluated at 72 hours had serum asparaginase activity levels > 0.4 International Units/mL [see Clinical Studies].
The safety and efficacy of ERWINAZE was established in Study 1, a single-arm, multi-center, open-label, safety and clinical pharmacology trial. Additional safety data was obtained in the ERWINAZE Master Treatment Protocol (EMTP), an expanded access program [see ADVERSE REACTIONS]. Study 1 enrolled patients treated on National Cancer Institute (NCI)-sponsored cooperative group ALL protocols who were unable to continue to receive pegaspargase due to hypersensitivity reactions. The main outcome measure was determination of the proportion of patients who achieved a serum trough asparaginase level greater than or equal to 0.1 International Units/ mL. Serum trough asparaginase activity ≥ 0.1 International Units/ mL has been demonstrated to correlate with asparagine depletion (asparagine < 0.4 mcg/mL or 3 μM) and to serum levels that predict clinical efficacy. Patients received ERWINAZE 25,000 International Units/m² intramuscularly for two weeks (total 6 doses) as a replacement for each scheduled dose of pegaspargase remaining on their original treatment protocol.
Fifty-eight patients were enrolled in Study 1, of these 48 were evaluable for the main outcome measure based on availability of pharmacokinetic samples in course 1. The median age was 11 years (2 to 18 years); 59% were male, 78% were White, 10% were Black/African American, 5% were Asian, and 7% were other or unknown. A total of 35% were Hispanic or Latino.
Study 1 met its main outcome measure of demonstrating that greater than 50% of the patients achieved the pre-specified trough asparaginase activity level of ≥ 0.1 International Units/ mL at 48 or 72 hours following the third dose. Results for the main outcome measure and for an exploratory analysis using a higher cut-off (trough serum asparaginase activity levels ≥ 0.4 International Units/mL are presented in Table 3 [see CLINICAL PHARMACOLOGY].
Table 3: Proportion of Patients in Study 1 with
Sustained Asparaginase Activity
|Trough sampling time post Dose 3||Main Outcome Proportion (n/N) and 95% CI with asparaginase activity ≥ 0.1 IU/mL||Exploratory Analysis Proportion (n/N) and 95% CI with asparaginase activity ≥ 0.4 IU/mL|
95% CI: 90%, 100%
95% CI: 64%, 90%
95% CI: 77%, 100%
95% CI: 18%, 65%
Last reviewed on RxList: 3/21/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Erwinaze Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.