FDA Approves Additional Dosing Schedule for Rylaze in ALL and LBL

FDA

The FDA has approved a supplemental biologics license application to add a Monday/Wednesday/Friday (MWF) intramuscular dosing schedule for asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze).¹

In June 2021, Rylaze was approved for use as part of a chemotherapy regimen in adult and pediatric patients aged 1 month or older with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) who have developed hypersensitivity to E. coli-derived asparaginase. At that time point, the approved dosing schedule was 25 mg/m² given intramuscularly every 48 hours.²

The new dosing option was greenlit by the regulatory agency under the FDA Real-Time Oncology Review program based on findings from the intramuscular administration portion of the phase 2/3 JZP458-201 trial (NCT04145531). Data from this trial also served as the basis for the initial approval of the drug.

Among the 225 evaluable patients on the trial, the median age was 10 years (range, 1-25 years). Moreover, 61% were male and 69% were White. Eighty-three percent of patients experienced a hypersensitivity reaction that was grade 3 or higher to pegaspargase; 7% (n = 15) reported silent inactivation.

Data demonstrated that a dosing regimen of 25 mg/m² given intramuscularly on Monday morning and Wednesday morning, and 50 mg/m² given on Friday afternoon resulted in a positive benefit-to-risk profile, with 90% or more of the patients achieving nadir serum asparaginase activity of at least 0.1 U/mL by simulation.

"The expansion of the Rylaze label to include a M/W/F dosing schedule provides another option to support patients in completing their planned asparaginase treatment regimen. The benefit of completing the full course of asparaginase has been shown in various publications, and discontinuation of asparaginase has been associated with inferior disease-free survival," Dr Luke Maese, associate professor at the University of Utah, Primary Children's Hospital and Huntsman Cancer Institute, stated in a press release. "Rylaze is an effective and reliable treatment option for patients with ALL and LBL that have developed hypersensitivity to an E. coli-derived asparaginase."

In the open-label, multicohort, multicenter trial, Rylaze was given at several dosages and routes of administration every Monday, Wednesday, and Friday for a total of 6 doses to replace each dose of pegaspargase.

Regarding safety, in 167 patients who were given Rylaze intramuscularly on the M/W/F schedule for 6 doses as a replacement for a single dose of pegaspargase as a component of multiagent chemotherapy. The median age of patients was 11 years (range, 1-25); most patients were male (57%) and White (68%). Patients received a median of 4 courses of Rylaze (range, 1-14); 65% of patients received at least 4 courses.

A fatal adverse reaction occurred in 1 patient treated with the agent 25/25/25 mg/m² dosage. Serious toxicities occurred in 60% of patients who received the recommended dosages of the agent.

The most common nonhematological serious adverse reactions reported in at least 5% of patients included febrile neutropenia, infection, drug hypersensitivity, pyrexia, nausea, dehydration, stomatitis, acute kidney injury, pancreatitis, diarrhea, and viral infection.

Permanent discontinuation because of a toxicity occurred in 10% of patients who received Rylaze intramuscularly at the recommended dosages. Adverse reactions that led to permanent discontinuation included pancreatitis (5%), drug hypersensitivity (4%), and infection (1%).

All participants who received with the recommended dosages of the agent as a component of multiagent chemotherapy experienced neutropenia, anemia, or thrombocytopenia.

The most frequently experienced nonhematological adverse reactions observed in patients were abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage, stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia.

References

1. Jazz Pharmaceuticals announces US FDA approval of Monday/Wednesday/Friday intramuscular dosing schedule of Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn). News release. Jazz Pharmaceuticals plc. November 18, 2022. Accessed November 18, 2022. http://bit.ly/3ggtECi
2. Rylaze (asparaginase erwinia chrysanthemi [recombinant]-rywn). Prescribing information; Jazz Pharmaceuticals plc; 2022. Accessed November 18, 2022. https://pp.jazzpharma.com/pi/rylaze.en.USPI.pdf