FDA Approval Sought for Rylaze in Adult/Pediatric Acute Lymphoblastic Lymphoma and Lymphoblastic Lymphoma

A supplemental biologics license application (sBLA) has been submitted to the FDA for a Monday/Wednesday/Friday (M/W/F) intramuscular (IM) dosing schedule of asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) for use in combination with a chemotherapy regimen to treat adults patients and pediatric patients 1 month or older with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) who have developed hypersensitivity to E. coli-derived asparaginase, according to a press release issued by Jazz Pharmaceuticals plc.¹

Asparaginase erwinia chrysanthemi (recombinant)-rywn is already an FDA-approved treatment for patient population based on findings from a phase 2/3 single-arm, open-label, multicenter, dose confirmation study (NCT04943952) of 102 patients. In the study, the recommended dosing for the agent was determined and the drug was shown to reach the target level of asparaginase activity in 94% of patients.^2,3

In terms of safety, adverse events (AEs) from the drug occurred in more than 15% of patients. The most common AEs observed were abnormal liver tests, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia. One patient had a fatal reaction to the therapy, and serious AEs were observed in 55% of patients. Of the serious AEs, those observed most frequently were febrile neutropenia, dehydration, pyrexia, stomatitis, diarrhea, drug hypersensitivity, infection, nausea, and viral infection.

Overall, 9% of patients permanently discontinued treatment as a result of AEs. Hypersensitivity led to permanent discontinuation in 6% patients, and 3% discontinued due to infection.

“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," said Rob Iannone, MD, MSCE, executive vice president, global head of research and development of Jazz Pharmaceuticals, in a press release.¹

The currently approved dosing schedule for asparaginase erwinia chrysanthemi (recombinant)-rywn is 25mg/m² IM on Monday and Wednesday, and 50 mg/m² given on Friday. The sBLA for the new dosing scheduling is also supported by the phase 2/3 trial, which studied 3 dosing regimens asparaginase erwinia chrysanthemi including, 25 mg/m² administered M/W/F in cohort 1a, 37.5 mg/m² administered M/W/F in cohort 1b, and cohort 1c was treated with asparaginase erwinia chrysanthemi (recombinant)-rywn 25 mg/m² administered Monday and Wednesday and 50 mg/m² administered on Friday. A positive benefit-risk profile was observed with the cohort 1c dosing schedule. Safety at the cohort 1c dosing schedule was also consistent with the known profile of asparaginase erwinia chrysanthemi (recombinant)-rywn in combination with chemotherapy.^1,2

“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, added Iannone.¹

The sBLA submission for asparaginase erwinia chrysanthemi (recombinant)-rywn will be reviewed under the Real-Time Oncology Review program, an initiative of FDA's Oncology Center of Excellence that aims to carry out efficient reviews of safe and effective cancer treatments.

_References:

_{1. Jazz Pharmaceuticals completes U.S. FDA supplemental biologics license application for Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) Monday/Wednesday/Friday dosing schedule. News release. Jazz Pharmaceuticals. February 2, 2022. https://bit.ly/3shxvkm}

_{2. Jazz Pharmaceuticals announces U.S. FDA approval of Rylaze™ (asparaginase erwinia chrysanthemi (recombinant)-rywn) for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma. News release. June 30, 2021. Accessed June 30, 2021. https://bit.ly/2UM6IzG}

_{3. FDA approves component of treatment regimen for most common childhood cancer. FDA. FDA Website. June 30, 2021. Accessed June 30, 2021. https://bit.ly/3hqFvKw}