On November 18, the U.S. Food and Drug Administration (FDA) approved a new Monday/Wednesday/Friday dosing regimen for asparaginase erwinia chrysanthemi (recombinant)-rywn (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.
The FDA approved asparaginase erwinia chrysanthemi (recombinant)-rywn in June 2021 as a component of a multiagent chemotherapeutic regimen for acute lymphoblastic leukemia and lymphoblastic lymphoma in adult and pediatric patients aged 1 month or older who have developed hypersensitivity to Escherichia coli–derived asparaginase.
The pharmacokinetics of the recombinant agent were evaluated in 225 patients in Study JZP458-201 (ClinicalTrials.gov identifier NCT04145531), an open-label multicenter trial in which the therapy was administered at various dosages and routes, and the results were used to develop a model to predict serum asparaginase activity at various time points.
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% confidence interval [CI] = 90.4%–92.8%) after the 25 mg/m2 Wednesday morning dose 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 asparaginase erwinia chrysanthemi (recombinant)-rywn as a component of multiagent chemotherapy experienced neutropenia, anemia, or thrombocytopenia. The most common nonhematologic adverse reactions (incidence > 20%) 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 which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews may be ongoing at the other regulatory agencies.
This review also used the Real-Time Oncology Review 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.
