On June 30, 2021, the U.S. Food and Drug Administration (FDA) approved asparaginase Erwinia chrysanthemi (recombinant)-rywn (Rylaze) as a component of a multiagent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma in adult and pediatric patients aged 1 month or older who have developed hypersensitivity to Escherichia coli–derived asparaginase. The only other FDA-approved drug for such patients with allergic reactions has been in global shortage for years.
“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 for Pediatric Oncology in the FDA’s Oncology Center of Excellence. “[This] approval may provide a consistently sourced alternative to a pivotal component of potentially curative therapy for children and adults with this type of leukemia.”
Study Details
Efficacy was evaluated in Study JZP458-201 (ClinicalTrials.gov identifier NCT04145531), an open-label, multicohort, multicenter trial in 102 patients with ALL or lymphoblastic lymphoma 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 to 24 years. Patients received recombinant Erwinia asparaginase intramuscularly at various dosages.
The main efficacy outcome measure was demonstration of achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 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 recombinant Erwinia asparaginase was 93.6% (95% confidence interval = 92.6%–94.6%).
The most common adverse reactions (incidence > 20%) were abnormal liver test, 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 recombinant Erwinia asparaginase is 25 mg/m2 administered intramuscularly every 48 hours for the required duration of asparaginase activity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with Health Canada, where the application review is pending.
Recombinant Erwinia asparaginase had previously been granted Fast Track and Orphan Drug designations for this indication.
