European Commission Approves Enrylaze for ALL and Lymphoblastic Lymphoma

The European Commission has granted marketing authorization for Enrylaze (JZP458; Rylaze in United States/Canada), a recombinant Erwinia asparaginase or crisantaspase for use as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month and older who developed hypersensitivity or silent inactivation to Escherichia coli (E. coli)–derived asparaginase.¹ 

The approval is based on data from the phase 2/3 JZP458-201 trial (NCT04145531), which demonstrated achievement and maintenance of nadir serum asparaginase activity (NSAA) levels at or above 0.1 U/mL with either intravenous (IV) or intramuscular (IM) administration in 228 pediatric and adult patients with ALL and LBL and hypersensitivity or silent inactivation to E. coli-derived asparaginase.

Results showed that 89.8% (95% CI, 82.1%-97.5%) and 40% (95% CI, 26.4%-53.6%) of patients maintained NSAA of at least 0.1 U/mL 48- and 72-hours post-dose with IV administration of Enrylaze at a dose of 25/25/50 mg/m2 on Monday, Wednesday, and Friday. IM administration of JZP458 at the same dosing schedule led to sustained asparagine activity in 95.9% of patients 48 hours post-dose (95% CI, 90.4%-100.0%) and 89.8% of patients 72 hours post-dose (95% CI, 81.3%-98.3%).

“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,” Professor Carmelo Rizzari, Department of Pediatrics, University of Milano-Bicocca, Head of the Pediatric Hematology Oncology Unit, Foundation IRCCS San Gerardo dei Tintori, Monza, Italy, stated in a news release. “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 Enrylaze now provides an important option to support patients in completing their planned asparaginase treatment regimen.”

In June 2021, the FDA approved Rylaze as part of a chemotherapy regimen for the treatment of pediatric and adult patients with ALL and LBL who are allergic to the E. coli-derived asparaginase products.² In November 2022, the FDA approved a supplemental biologics license application to add a Monday/Wednesday/Friday IM dosing schedule for Rylaze.³

Treatment with Enrylaze resulted in a similar safety profile in patients with ALL/LBL who previously received asparaginase with multi-agent chemotherapy. The most frequent adverse effects (AEs) were anemia, vomiting, thrombocytopenia, neutropenia, nausea, febrile neutropenia, fatigue, pyrexia, decreased appetite, increased transaminase, abdominal pain, decreased white blood cell count, headache, diarrhea, and decreased lymphocyte count. The most common serious AEs were febrile neutropenia, pyrexia, vomiting, sepsis, medicinal product hypersensitivity, nausea, and pancreatitis.¹

“This approval is a testament to Jazz’s commitment to developing an Erwinia-derived asparaginase using innovative recombinant technology to deliver a scalable supply, and we look forward to making Enrylaze available to those who need it,” Robert Iannone, MD, MSCE, executive vice president, global head of research and development of Jazz Pharmaceuticals, said. “Healthcare professionals in the European Union will now have access to a new, recombinant Erwinia-derived asparaginase with multiple dosing and administration options to address their patients' individual needs, which allows them to complete their treatment program as prescribed.”

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://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-receives-european-commission-approval
2. FDA approves component of treatment regimen for most common childhood cancer. News release. FDA. June 30, 2021. Accessed September 22, 2023. https://www.prnewswire.com/news-releases/fda-approves-component-of-treatment-regimen-for-most-common-childhood-cancer-301323754.html
3. 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 September 22, 2023. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval