FDA Approves Second Dosing Regimen for Asparaginase Erwinia Chrysanthemi (Recombinant)-Rywn
On November 18, 2022, the U.S. Food and Drug Administration (FDA) approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-new-dosing-regimen-asparaginase-erwinia-chrysanthemi-recombinant?utm_medium=email&utm_source=govdelivery) a Monday-Wednesday-Friday dosing option for asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze®). Under the alternative regimen, patients receive 25 mg/m2 intramuscularly on Monday and Wednesday mornings and 50 mg/m2 intramuscularly on Friday afternoons. It also is approved at a dose of 25 mg/m2 intramuscularly every 48 hours.
FDA approved (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-asparaginase-erwinia-chrysanthemi-recombinant-leukemia-and-lymphoma?utm_medium=email&utm_source=govdelivery) 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 one month or older who have developed hypersensitivity to E. coli-derived asparaginase.
The agent’s pharmacokinetics were evaluated in 225 patients in study JZP458-201 (NCT04145531), an open-label, multicenter trial in which asparaginase erwinia chrysanthemi (recombinant)-rywn was administered at various dosages and routes. Efficacy was defined as achievement and maintenance of nadir serum asparaginase activity (NSAA) above a 0.1 U/ml level in simulations with a virtual population. Using a model to predict serum asparaginase activity at various time points, the simulations predicted that for the Monday-Wednesday-Friday dosing regimen, the proportion of patients maintaining at least 0.1 U/ml of NSAA was 91.6% (95% CI = 90.4%, 92.8%) after the 25 mg/m2 Wednesday morning dose of asparaginase erwinia chrysanthemi (recombinant)-rywn and 91.4% (95% CI = 90.1%, 92.6%) after the 50 mg/m2 Friday afternoon dose.
All patients treated with the recommended asparaginase erwinia chrysanthemi (recombinant)-rywn dosages as a component of multiagent chemotherapy experienced neutropenia, anemia, or thrombocytopenia. The most common nonhematologic adverse reactions reported in more than 20% of patients treated with asparaginase erwinia chrysanthemi (recombinant)-rywn were abnormal liver tests, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.
The review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, 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.
The review used the Real-Time Oncology Review (https://www.fda.gov/about-fda/oncology-center-excellence/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.
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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).