FDA Approves Asparaginase Erwinia Chrysanthemi (Recombinant)-Rywn for ALL and LBL

Acute lymphoblastic leukemia.

The FDA granted approval to asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze™, Jazz Pharmaceuticals, Inc.) as part of a multi-agent chemotherapeutic regimen for patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) who have developed hypersensitivity to E. coli-derived asparaginase. Asparaginase erwinia chrysanthemi (recombinant)-rywn is an alternative to the only other FDA-approved drug for patients with this allergic reaction, which has been in short supply for a number of years.

"L-asparaginase is an important component of ALL therapy and the inability to receive asparaginase secondary to hypersensitivity has been associated with poor patient outcomes," wrote Luke Maese, DO, Assistant Professor at the University of Utah School of Medicine, and colleagues, in the abstract for the ongoing phase II/III JZP458-201 study (NCT04145531), on which the approval was based. "Alternative options for patients after hypersensitivity reactions are needed."

The open-label multi-cohort multicenter trial enrolled 102 patients with ALL or LBL with hypersensitivity to E. coli-derived asparaginase. Patients received asparaginase erwinia chrysanthemi (recombinant)-rywn intramuscularly. The doses were based on how many courses of asparaginase remained in the patients' planned treatment; enrolled patients needed at least one course of asparaginase remaining in their treatment plan in order to receive asparaginase erwinia chrysanthemi (recombinant)-rywn treatments. The main efficacy outcome measure was demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA), above the level of 0.1 U/mL.

The results, after modeling and simulations, were that for a dosage of 25 mg/m² that was administered every 48 hours, 93.6% of patients maintained NSAA ≥ 0.1 U/mL 48 hours after an administered dose of asparaginase erwinia chrysanthemi (recombinant)-rywn.

The most common adverse reactions occurring in more than 20% of patients were abnormal liver test, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia.

"This is a pivotal, open-label, multicenter, dose confirmation, and pharmacokinetic study," concluded Dr. Maese and colleagues in their May 2020 published meeting abstract in the Journal of Clinical Oncology. "The trial is active and enrolling."

The recommended dose of asparaginase erwinia chrysanthemi (recombinant)-rywn is 25 mg/m², administered intramuscularly every 48 hours for the required duration of asparaginase activity, as replacement for a for long-acting asparaginase product.

For More Information

Maese L, Rau RE, Raetz EA, et al (2020). A phase II/III study of JZP-458 in patients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) who are hypersensitive to E. coli-derived asparaginases. J Clin Oncol, 38(suppl_15). Abstract TPS7568. DOI:10.1200/JCO.2020.38.15_suppl.TPS7568

Clinicaltrials.gov (2021). An open-label study of JZP-458 (RC-P) in patients with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). NLM identifier: NCT04145531.

Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) prescribing information (2021). Jazz Pharmaceuticals, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761179s000lbl.pdf

US Food & Drug Administration (2021). FDA approves component of treatment regimen for most common childhood cancer. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-component-treatment-regimen-most-common-childhood-cancer

US Food & Drug Administration (2021). FDA approves asparaginase erwinia chrysanthemi (recombinant) for leukemia and lymphoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-asparaginase-erwinia-chrysanthemi-recombinant-leukemia-and-lymphoma

Image credit: Osaretin. Licensed under CC BY-SA 4.0