The manufacturer, Jazz Pharmaceuticals, recently announced that the company completed the submission of a sBLA to the FDA seeking approval for a Monday/Wednesday/Friday (M/W/F) IM dosing schedule for Rylaze (asparaginase erwinia chrysanthemi [recombinant]-rywn), for use 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 aged 1 month and older who have developed hypersensitivity to E coli–derived asparaginase. Rylaze is a recombinant erwinia asparaginase that uses a novel Pseudomonas fluorescens expression platform. The submission will be reviewed under the Real-Time Oncology Review (RTOR) program, an initiative of the FDA's Oncology Center of Excellence created for efficient review of safe and effective cancer treatments and follows Rylaze's initial approval under the RTOR program in June 2021.
Rob Iannone, MD, MSCE, executive vice president, global head of research and development of Jazz Pharmaceuticals, stated, "We were pleased Rylaze, a much-needed therapeutic option, was approved under the RTOR program while the clinical trial was ongoing. Our science-led and patient-focused development program has enabled us to deliver a clinically significant advancement for patients. With a dosing schedule of Rylaze administered 25/25/50 mg/m2 on Monday/Wednesday/Friday, patients maintain a clinically meaningful level of nadir serum asparaginase activity through the entire duration of treatment. We look forward to submitting two additional regulatory applications this year to ensure as many patients as possible can have access to a reliable and high-quality supply of this important therapy, including another regulatory application to FDA to support the intravenous route of administration and an additional application in Europe later this year."
The sBLA submitted by Jazz is supported by data from the three-cohort IM administration part of the phase II/III trial of Rylaze in adult and pediatric patients with ALL and LBL who have developed hypersensitivity to an E coli–derived asparaginase. The trial studied three dosing regimens of Rylaze, with cohort 1a receiving 25 mg/m2 administered M/W/F, cohort 1b receiving 37.5 mg/m2 administered M/W/F, and cohort 1c receiving 25 mg/m2 administered Monday and Wednesday and 50 mg/m2 administered on Friday. Initial results disclosed that in cohort 1c, a dosing regimen of Rylaze administered 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday demonstrated a positive benefit-to-risk profile, showing that Rylaze maintains a clinically meaningful level of nadir serum asparaginase activity >0.1 IU/mL at both 48 and 72 hours (from Friday to Monday). In addition, the safety profile of Rylaze was consistent with the reported safety information for patients with ALL/LBL receiving asparaginase with combination chemotherapy. Initial results from the trial were presented at the 63rd American Society of Hematology Annual Meeting in December 2021.
The sBLA follows FDA approval of Rylaze in June 2021 under the RTOR program. Rylaze was also granted orphan drug designation for the treatment of ALL/LBL in June 2021 and was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in July 2021.
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