FDA D.I.S.C.O. Burst Edition: FDA approves a new dosing regimen for asparaginase erwinia chrysanthemi (recombinant)
Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide another quick update on a recent FDA cancer drug approval.
On November 18, 2022, the FDA approved a new Monday-Wednesday-Friday dosing regimen for asparaginase erwinia chrysanthemi (recombinant)-rywn (brand name Rylaze). 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 and lymphoblastic lymphoma 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, 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 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 nadir serum asparaginase activity of greater than or equal to 0.1 U/mL was 91.6% after the 25 mg/m2 Wednesday morning dose of Rylaze and 91.4% 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 occurring in more than 20% of 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.
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. The application reviews may be ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application.
Full prescribing information for these approvals can be found at Drugs@FDA: FDA-Approved Drugs.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at MedWatch: The FDA Safety Information and Adverse Event Reporting Program.
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