The Food and Drug Administration (FDA) has approved Rylaze™ (asparaginase erwinia chrysanthemi [recombinant]-rywn) as part of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month of age and older who have developed hypersensitivity to E. coli-derived asparaginase.
Asparaginase erwinia chrysanthemi (recombinant)-rywn is an asparagine specific enzyme designed to catalyze the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The product is produced by fermentation of a genetically engineered Pseudomonas fluorescens bacterium containing the DNA which encodes for asparaginase Erwinia chrysanthemi. The depletion of plasma asparagine leads to the killing of leukemic cells.
The approval was based on data from an ongoing multicenter, single-arm, open-label phase 2/3 trial (ClinicalTrials.gov Identifier: NCT04145531) that evaluated the efficacy, safety and tolerability of Rylaze as a component of a multi-agent chemotherapeutic regimen in 102 patients with ALL or LBL who have developed hypersensitivity to E. coli-derived asparaginase. The median age of the patients was 10 years (range, 1 to 24 years).
The primary endpoint was the response rate, defined as the proportion of patients with the last 72-hour nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL. Results of modeling and simulations showed that 93.6% (95% CI, 92.6-94.6) of patients maintained NSAA levels greater than or equal to 0.1 U/mL at 48 hours after a dose of Rylaze 25mg/m2 administered intramuscularly every 48 hours.
Regarding safety, the most common adverse reactions were abnormal liver test, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia. Rylaze is contraindicated in patients with a history of serious pancreatitis, serious thrombosis, or serious hemorrhagic events during previous asparaginase therapy.
Commenting on the accelerated approval, Gregory Reaman, MD, associate director for pediatric oncology in the FDA’s Oncology Center of Excellence, said: “It is extremely disconcerting to patients, families and providers when there is a lack of access to critical drugs for treatment of a life-threatening, but often curable cancer, due to supply issues. Today’s approval may provide a consistently sourced alternative to a pivotal component of potentially curative therapy for children and adults with this type of leukemia.”
Rylaze will be supplied as single-dose vials containing 10mg/0.5mL solution of asparaginase erwinia chrysanthemi (recombinant)-rywn and is expected to be available in mid-July 2021.
- Jazz Pharmaceuticals announces U.S. FDA approval of Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma. [press release]. Dublin, Ireland: Jazz Pharmaceuticals plc; June 30, 2021.
- FDA approves component of treatment regimen for most common childhood cancer. [press release]. Silver Spring, MD: US Food and Drug Administration; June 30, 2021.
- Rylaze [package insert]. Palo Alto, CA; Jazz Pharmaceuticals, Inc.; 2021.