Jazz Pharmaceuticals Receives European Commission Approval for Enrylaze® (a recombinant Erwinia asparaginase or crisantaspase) for the Treatment of Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
"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," said Professor
Enrylaze may be given by both intravenous infusion (IV) and intramuscular injection (IM) and is dosed on either alternate days (every 48 hours) or via a Monday/Wednesday/Friday (MWF) dosing schedule.1 The use of recombinant technology to manufacture Enrylaze delivers a scalable supply – able to meet global demand, and a ready-to-use solution that avoids the need for reconstitution in the clinic.2
"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," said
The study showed that for the IV administration of JZP458 (a recombinant Erwinia asparaginase or crisantaspase) (25/25/50 mg/m2 MWF), the proportion of patients maintaining NSAA ≥ 0.1 U/mL at 48 hours after a dose was 89.8% (95% CI: 82.1%, 97.5%) and 40% at 72 hours post-dose (95% CI: 26.4%, 53.6%). The IM administration of JZP458 (25/25/50 mg/m2 MWF) achieved sustained asparagine activity in 95.9% of patients at 48 hours after a dose (95% CI: 90.4%, 100.0%) and 89.8% of patients at 72 hours post-dose (95% CI: 81.3%, 98.3%). The other dosing schedules were based on interpolation from pharmacokinetic (PK) and response rates observed with the very similar investigated regimens.1
Overall, the safety profile of JZP458 was consistent with the reported safety information for patients with ALL/LBL receiving asparaginase with combination chemotherapy.1,3 The most common adverse reactions were anemia, vomiting, thrombocytopenia, neutropenia, nausea, febrile neutropenia, fatigue, pyrexia, decreased appetite, transaminase increased, abdominal pain, white blood cell count decreased, headache, diarrhea, and lymphocyte count decreased. The most frequent serious adverse reactions were febrile neutropenia, pyrexia, vomiting, sepsis, medicinal product hypersensitivity, nausea, and pancreatitis.1
The European Commission approval extends to all
For a full list of side effects and information on dosage and administration, contraindications, and other precautions when using Enrylaze, please refer to the Summary of Product Characteristics for further information.
About Enrylaze® (JZP458) Enrylaze, also known as JZP458 and approved as Rylaze® in
About Study JZP458-201
About Acute Lymphoblastic Leukemia (ALL)
Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that can progress quickly if not treated.6,7 ALL is the most common childhood malignancy, accounting for 80% of leukemia diagnoses in children, compared to 20% of adults.8 Long-term survival rates for pediatric patients have improved significantly over the last few decades, which is in part a result of crafting effective combinations of multi-agent chemotherapeutics with an asparaginase backbone.9 The estimated overall incidence of ALL and lymphoblastic lymphoma (LBL) in
Asparaginase is a core component of multi-agent chemotherapeutic regimens in ALL,12 however, up to 30% of patients develop hypersensitivity to E. coli-derived asparaginase,13 necessitating treatment discontinuation or a switch to a non-E. coli-derived asparaginase preparation.14 Patients not receiving asparaginase due to hypersensitivities and those not receiving all prescribed doses have been shown to have poor outcomes.2,15
About Lymphoblastic Lymphoma (LBL)
Lymphoblastic Lymphoma (LBL) is a rare, fast-growing, aggressive subtype of non-Hodgkin's lymphoma (NHL), which is very rare in adults and is most often seen in teenagers and young adults under the age of 35.16,17 LBL is a type of high-grade lymphoma – which means the lymphoma grows quickly with early spread to different parts of the body.17 LBL is the second most common type of NHL in childhood and adolescence, accounting for 25-35% of cases.18
About Jazz Pharmaceuticals
Head of Strategic Brand Engagement
Vice President, Head, Investor Relations
2 Maese L, Rizzari C, Coleman R, et al. Can recombinant technology address asparaginase Erwinia chrysanthemi shortages? Pediatr Blood Cancer. 2021;68(10):e29169. DOI 10.1002/pbc.29169.
3 Maese L, Mignon L, et al. Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2/3 AALL1931 study. Blood. 2023; 141 (7): 704–712.
Updated 2021. Accessed
5 Rylaze Product Monograph. Updated
8 Chennamadhavuni A, et al. Leukemia. In: StatPearls [Online].
9 Neaga A, et al. Why do children with acute lymphoblastic leukemia fare better than adults? Cancers (
10 Hoelzer D, et al. Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v69–v82.
11 GBD. The global burden of childhood and adolescent cancer in 2017: an analysis of the Global Burden of Disease Study 2017. Lancet Oncol. 2019;20:1211–1225.
12 Salzer W, Bostrom B, Messinger Y, et al. Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia. Leuk Lymphoma. 2018;59(8):1797-1806. DOI 10.1080/10428194.2017.1386305.
13 van der Sluis IM, et al. Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica. 2016;101(3):279–285.
14 Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma. 2016;57(4):748-757. DOI 10.3109/10428194.2015.1101098.
15 Gupta S, Wang C, Raetz EA, et al. Impact of asparaginase discontinuation on outcome in childhood acute lymphoblastic leukemia: a report from the children's oncology group. J Clin Oncol. 2020;38(17):1897-1905. DOI 10.1200/JCO.19.03024.
18 Burkhardt B, et al. Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. Br
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