On June 30, 2021, the FDA accelerated the approval of asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze; Jazz Pharmaceuticals), an asparagine-specific enzyme, as a component of a multidrug chemotherapy regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in patients aged ≥1 months with hypersensitivity to Escherichia coli–derived asparaginase. The FDA granted asparaginase erwinia a fast-track review and an orphan drug designation for this indication.
“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,” said Gregory Reaman, MD, Associate Director of Pediatric Oncology in the FDA’s Oncology Center of Excellence. “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.”
The FDA approved erwinia chrysanthemi based on results of the JZP458-201 study, an open-label, multicohort, multicenter clinical trial of 102 patients (median age, 10 years; range, 1-24 years) with ALL or LBL and hypersensitivity to asparaginase caused by E coli infection, as part of a multidrug chemotherapy regimen. Erwinia chrysanthemi was administered intramuscularly, at various dosages.
The primary end point was achievement and maintenance of nadir serum asparaginase activity >0.1 U/mL. The results of modeling and simulations showed that for a dosage of 25 mg/m2 administered every 48 hours, the proportion of patients maintaining nadir serum asparaginase activity ≥0.1 U/mL at 48 hours after a dose of erwinia chrysanthemi was 93.6% (95% CI, 92.6%-94.6%).
The most common (>20%) adverse reactions were abnormal liver test, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia.