The FDA has approved a new dosing schedule of Rylaze for patients with acute lymphoblastic leukemia and lymphoblastic lymphoma.
The FDA has granted approval to a supplemental biologics license application to add a Monday/Wednesday/Friday intramuscular dosing schedule of asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) in combination with a chemotherapy regimen for the treatment of adult 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.1
Previously, asparaginase erwinia chrysanthemi (recombinant)-rywn was approved by the FDA for this patient population based on findings from the phase 2/3 JZP458-201 trial (NCT04943952). The trial evaluated 102 patients and determined the recommended dose for the agent which reached the target level of asparaginase activity in 94% of patients.2,3
"With the addition of a Monday/Wednesday/Friday dosing schedule for Rylaze, patients will have another dosing option, which provides sustained asparaginase activity throughout the entire course of Rylaze treatment," said Rob Iannone, MD, MSCE, executive vice president, global head of research and development of Jazz Pharmaceuticals plc, in the press release. "Jazz has been consistently committed to ensuring access to the reliable, high-quality supply of this important therapy so patients and healthcare providers have the opportunity to complete the full course of asparaginase therapy. As part of our efforts to improve patient and healthcare provider experience with Rylaze, we have evaluated additional dosing and administration options, and are also seeking approval for Rylaze globally."
In the phase 2/3, single-arm, open-label, multicenter, dose confirmation study, the dosing regimen consisted of giving asparaginase erwinia chrysanthemi (recombinant)-rywn at 25 mg/m2 given intramuscularly on Monday morning and Wednesday morning, and 50 mg/m2 given on Friday afternoon led to a positive benefit-to-risk profile. Ninety percent or more of the patients achieved nadir serum asparaginase activity of at least 0.1 U/mL by simulation.
Safety findings showed that adverse events (AEs) from the drug occurred in more than 15% of patients. The most common AEs included 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 The most frequently observed serious AEs were febrile neutropenia, dehydration, pyrexia, stomatitis, diarrhea, drug hypersensitivity, infection, nausea, and viral infection. Additionally, 9% of patients permanently discontinued treatment as a result of AEs, hypersensitivity led to permanent discontinuation in 6% patients, and infection led to discontinuation in 3%.
Overall, the safety profile of asparaginase erwinia chrysanthemi (recombinant)-rywn was consistent with previously reported safety information of patients with ALL/LBL receiving asparaginase with combination chemotherapy. Further, no new safety signals were observed in the trial.
"The expansion of the Rylaze label to include a Monday/Wednesday/Friday 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," said Luke Maese, MD, associate professor at the University of Utah, Primary Children's Hospital and Huntsman Cancer Institute, in the 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."