JZP458 Receives EU Greenlight for ALL/Lymphoblastic Lymphoma

"The approval of [JZP458] now provides an important option to support patients in completing their planned asparaginase treatment regimen," according to Carmelo Rizzari, a professor in the Department of Pediatrics at University of Milano-Bicocca, and head of the Pediatric Hematology Oncology Unit at Foundation IRCCS San Gerardo dei Tintori in Monza, Italy.

A recombinant Erwinia asparaginase or crisantaspase, JZP458 (Enrylaze), has received approval from the European Commission as part of a multi-agent chemotherapy strategy in a population of adult and pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) with a hypersensitivity or silent inactivation to E. coli–derived asparaginase, according to a press release from Jazz Pharmaceuticals.¹

The Erwinia-derived asparaginase was created via next-generation recombinant technology that appears to have comparable safety vs other asparaginase options. JZP458 can be administered via intravenous infusion or intramuscular injection using an alternating day schedule, or on Monday, Wednesday, and Friday.

The approval was based on findings from a phase 2/3 study (NCT04145531) from the Children’s Oncology Group, which included 228 adult and pediatric patients with ALL and LBL with hypersensitivity or silent inactivation to E. coli-derived asparaginase. Investigators reported that 89.8% (95% CI, 82.1%-97.5%) of patients maintained a nadir serum asparaginase activity (NSAA) level of 0.1 U/mL or more at 48 hours after treatment along with 40% (95% CI, 26.4%-53.6%) after 72 hours.

Common adverse effects associated with JZP458 included anemia, vomiting, thrombocytopenia, neutropenia, nausea, febrile neutropenia, fatigue, pyrexia, appetite decrease, transaminase increase, abdominal pain, white blood cell count decrease, headache, diarrhea, and lymphocyte count decrease.

“Asparaginase is a core component of multi-agent chemotherapeutic regimens for the treatment of ALL, however, up to 30% of patients develop hypersensitivity to E. coli-derived asparaginase, resulting in a delay or disruption in treatment,” Carmelo Rizzari, a professor in the Department of Pediatrics at University of Milano-Bicocca, and head of the Pediatric Hematology Oncology Unit at Foundation IRCCS San Gerardo dei Tintori in Monza, Italy, said in a press release on the findings.

“The ability to complete a full course of asparaginase treatment is of critical importance when treating ALL and LBL, as it is strongly linked to improved outcomes for patients. The approval of [JZP458] now provides an important option to support patients in completing their planned asparaginase treatment regimen.”

The Committee for Medicinal Products for Human Use gave a positive opinion on JZP458 in July 2023 for the aforementioned patient population. Additionally, the FDA approved asparaginase Erwinia chrysanthemi (Rylaze) in November 2022 for those with ALL/LBL at a dose of 25 mg/m² intramuscularly on Monday and Wednesday morning and 50 mg/m² on Friday afternoons, or at 25 mg/m² every 48 hours.

References

1. Jazz Pharmaceuticals receives European Commission approval for Enrylaze® (a recombinant Erwinia asparaginase or crisantaspase) for the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. News release. Jazz Pharmaceuticals. September 21, 2023. Accessed September 22, 2023. https://bit.ly/3PR3cON
2. Jazz Pharmaceuticals receives CHMP positive opinion for JZP458 (a recombinant Erwinia asparaginase or crisantaspase) for the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. News Release. Jazz Pharmaceuticals plc. July 21, 2023. Accessed September 22, 2023. https://prn.to/3OrPsJq
3. FDA approves a new dosing regimen for asparaginase erwinia chrysanthemi (recombinant). News release. FDA. November 18, 2022. Accessed September 22, 2023. bit.ly/3XecGoP