FDA approves a new dosing regimen for asparaginase erwinia chrysanthemi (recombinant)

FDA
  • FLASCO
  • November 18, 2022

On November 18, 2022, the Food and Drug Administration approved a new Monday-Wednesday-Friday dosing regimen for asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze, Jazz Pharmaceuticals). Under the new regimen, patients should receive 25 mg/m2 intramuscularly on Monday and Wednesday mornings, and 50 mg/m2 intramuscularly on Friday afternoon. It also is approved to be administered every 48 hours at a dose of 25 mg/m2 intramuscularly.

FDA approved Rylaze in June 2021 as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.

The pharmacokinetics of Rylaze were evaluated in 225 patients in Study JZP458-201 (NCT04145531), an open-label multicenter trial in which Rylaze was administered at various dosages and routes, and the results were used to develop a model to predict serum asparaginase activity at various timepoints.

The determination of efficacy was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL by simulation in a virtual population. The results of simulations predicted that for the Monday-Wednesday-Friday dosing regimen, the proportion of patients maintaining NSAA ≥ 0.1 U/mL was 91.6% (95% CI: 90.4%, 92.8%) after the 25 mg/m2 Wednesday morning dose of Rylaze and 91.4% (95% CI: 90.1%, 92.6%) after the 50 mg/m2 Friday afternoon dose.

All patients treated with the recommended dosages of Rylaze as a component of multi-agent chemotherapy experienced neutropenia, anemia, or thrombocytopenia. The most common nonhematological adverse reactions (incidence > 20%) in patients were abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.

View full prescribing information for Rylaze.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Switzerland’s Swissmedic. The application reviews may be ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application.

Asparaginase erwinia chrysanthemi (recombinant)-rywn also has orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email [email protected].

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