Switching to ERWINAZE may sustain asparaginase activity following hypersensitivity to E. coli-derived asparaginase2

  • In Study 1 with intramuscular (IM) ERWINAZE, serum asparaginase activity was measured at 48 and 72 hours following the third dose2
  • In Study 2 with intravenous (IV) ERWINAZE, serum asparaginase activity was measured at 48 hours following the fifth dose and 72 hours following the sixth dose2
  • Serum asparaginase activity ≥0.1 IU/mL has been demonstrated to correlate with asparagine depletion and to serum levels that predict clinical efficacy2

Percentage of patients with sustained asparaginase activity 0.1 IU/mL2

Asparaginase activity with ERWINAZE®

Study Design

Study 1, a single-arm, multi-center, open-label safety and clinical pharmacology trial, was conducted in 58 ALL patients who were unable to continue PEG-asparaginase due to hypersensitivity reactions. The main outcome measure was the proportion of patients who achieved a serum trough asparaginase level ≥0.1 IU/mL after the third dose. Patients received IM ERWINAZE 25,000 IU/m2 for 2 weeks (total of 6 doses) as a replacement for each scheduled dose of PEG-asparaginase remaining on their original treatment protocol. The 95% confidence interval (CI) for the 48-hour post dose 3 measurement was 90, 100 and for the 72-hour post dose 3 measurement was 77, 100.2

Study 2 enrolled 30 patients being treated for ALL or lymphoblastic lymphoma following allergy to native E. coli asparaginase or PEG-asparaginase. The main outcome measure was the proportion of patients who achieved a serum trough asparaginase level ≥0.1 IU/mL 48 hours after the fifth dose. The secondary outcome measure was asparaginase level ≥0.1 IU/mL 72 hours after the sixth dose. Patients received IV ERWINAZE 25,000 IU/m2 for a total of 6 doses as a replacement for each scheduled dose of PEG-asparaginase remaining on their original treatment protocol. The 95% CI for the 48-hour post dose 5 measurement was 63, 95 and for the 72-hour post dose 6 measurement was 22, 66.2

Contraindications
ERWINAZE is contraindicated in patients with a history of:

  • Serious hypersensitivity reactions to ERWINAZE, including anaphylaxis
  • Serious pancreatitis with prior L-asparaginase therapy
  • Serious thrombosis with prior L-asparaginase therapy
  • Serious hemorrhagic events with prior L-asparaginase therapy

ERWINAZE may allow patients to continue asparaginase treatment following a hypersensitivity reaction to E. coli-derived asparaginase2

ERWINAZE is an immunologically distinct form of asparaginase2,3,16

78% of patients (693/893) in the EMTP trial completed their prescribed asparaginase regimen after switching to ERWINAZE2


Patients completing their prescribed asparaginase treatment regimen after switching to ERWINAZE

Study Design

The ERWINAZE Master Treatment Protocol (EMTP), an expanded access program, enrolled 1368 patients with ALL who received ERWINAZE after developing systemic hypersensitivity to an E. coli-derived asparaginase. Of these 1368 patients, safety data were received for 940 patients with a median age of 9 years (0 to 76 years). The breakdown by age was: ≤10 years, 537 (57%); >10 to <16, 234 (25%); ≥16 to <40, 147 (16%); ≥40, 9 (1%); missing information, 13 (1%). Patients received ERWINAZE according to several schedules and treatment center specifications with doses that ranged from 20,000 to 25,000 IU/m2. The routes of administration were intramuscular, n=852; intravenous, n=29; other or unknown, n=59. Safety data were derived from case report forms that collected adverse event information. The forms specifically requested information on occurrence of allergic reactions, thrombotic events, hemorrhagic events, hepatobiliary disorders, pancreatic disorders, and hyperglycemia.2,17

Indication
ERWINAZE® (asparaginase Erwinia chrysanthemi) for intramuscular injection (IM) or intravenous infusion (IV), 10,000 International Units (IU)/vial, is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase.

IMPORTANT SAFETY INFORMATION

Contraindications
ERWINAZE is contraindicated in patients with a history of:

  • Serious hypersensitivity reactions to ERWINAZE, including anaphylaxis
  • Serious pancreatitis with prior L-asparaginase therapy
  • Serious thrombosis with prior L-asparaginase therapy
  • Serious hemorrhagic events with prior L-asparaginase therapy

Warnings and Precautions
Hypersensitivity Reactions
After the use of ERWINAZE in clinical trials, grade 3 and 4 hypersensitivity reactions have occurred in 5% of patients. Administer in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis. If a serious hypersensitivity reaction occurs (including anaphylaxis), discontinue ERWINAZE and initiate appropriate therapy.

Pancreatitis
In clinical trials, 4% of patients reported pancreatitis with ERWINAZE therapy. Discontinue ERWINAZE for severe or hemorrhagic pancreatitis manifested by abdominal pain >72 hours and amylase elevation ≥2.0 x ULN. In case of mild pancreatitis, hold ERWINAZE until the signs and symptoms subside and amylase levels return to normal. After resolution, ERWINAZE therapy may be resumed.

Glucose Intolerance
In clinical trials, 5% of patients reported glucose intolerance, which in some cases may be irreversible. Monitor glucose levels at baseline and periodically during treatment. Administer insulin therapy as necessary in patients with hyperglycemia.

Thrombosis and Hemorrhage
Serious thrombotic events, including sagittal sinus thrombosis, have been reported in both E. coli and Erwinia-derived L-asparaginase therapy. The following coagulation proteins were decreased in the majority of patients after a 2-week course of ERWINAZE by intramuscular administration: fibrinogen, protein C activity, protein S activity, and anti-thrombin III. Discontinue ERWINAZE for a thrombotic or hemorrhagic event until symptoms resolve; after resolution, ERWINAZE therapy may be resumed.

Most Common Adverse Reactions
The most common adverse reactions (incidence 1% or greater) with ERWINAZE treatment are systemic hypersensitivity, hyperglycemia, transaminases abnormal, fever, pancreatitis, local reactions, vomiting, nausea, thrombosis, hyperbilirubinemia, abdominal pain/discomfort, and diarrhea.

Use in Specific Populations
Pregnancy and Lactation
ERWINAZE can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Females of reproductive potential should be advised to use effective contraception during treatment with ERWINAZE and for 3 months after the final dose. Since an indirect interaction between oral contraceptives and ERWINAZE cannot be ruled out, a method of contraception other than oral contraceptives should be used. Breastfeeding is not recommended during treatment with ERWINAZE and for 3 months after the last dose.

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