On June 30, 2021, the U.S. Food and Drug Administration (FDA) approved asparaginase erwinia chrysanthemi (recombinant)-rywn (RylazeTM) as a component of a multiagent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase.
Efficacy was evaluated in an open-label, multicohort, multicenter trial (JZP458-201, NCT04145531) in 102 patients with ALL or LBL with hypersensitivity to E. coli-derived asparaginase as a component of a multiagent chemotherapeutic regimen. The median age was 10 years with a range of 1–24 years. Patients received asparaginase erwinia chrysanthemi (recombinant)-rywn intramuscularly at various dosages.
The main efficacy outcome measure was demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above 0.1 U/ml. The results of modeling and simulations showed that for a dosage of 25 mg/m2 administered intramuscularly every 48 hours, the proportion of patients maintaining NSAA ≥ 0.1 U/ml at 48 hours after a dose of asparaginase erwinia chrysanthemi (recombinant)-rywn was 93.6% (95% CI = 92.6%, 94.6%).
The most common adverse reactions (> 20%) were abnormal liver enzymes, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia.
When replacing a long-acting asparaginase product, the recommended dosage of asparaginase erwinia chrysanthemi (recombinant)-rywn is 25 mg/m2 administered intramuscularly every 48 hours for the required duration of asparaginase activity.
The review was conducted under Project Orbis, an initiative of FDA’s 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 Health Canada.
The review used the Real Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application 10 months ahead of FDA’s goal date.
FDA granted the application fast-track designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions.
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 800-FDA-1088.