Pharma Focus Europe

Jazz Pharmaceuticals Granted European Commission Authorization for Enrylaze® in Treating Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Friday, September 22, 2023

Jazz Pharmaceuticals plc (Nasdaq: JAZZ) has recently obtained marketing authorization from the European Commission (EC) for Enrylaze® (JZP458), a recombinant Erwinia asparaginase, or crisantaspase. This approval permits the use of Enrylaze as a part of a multi-agent chemotherapeutic treatment for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in both adult and pediatric patients aged one month and older who have developed hypersensitivity or silent inactivation to E. coli-derived asparaginase.

Asparaginase is a critical component of multi-agent chemotherapy for ALL, but about 30% of patients develop hypersensitivity to E. coli-derived asparaginase, which can disrupt or delay their treatment. Enrylaze, previously approved as Rylaze® in the United States and Canada, offers an alternative asparaginase option. It is derived from Erwinia bacteria using advanced recombinant technology and exhibits a safety profile similar to other asparaginase products.

Professor Carmelo Rizzari, from the University of Milano-Bicocca, Italy, emphasized the importance of completing a full course of asparaginase treatment for improved patient outcomes, making Enrylaze a valuable option for such cases.

Enrylaze can be administered via intravenous infusion (IV) or intramuscular injection (IM) and follows either an alternate-day (every 48 hours) or a Monday/Wednesday/Friday (MWF) dosing schedule. Its recombinant production ensures a scalable supply, eliminating the need for reconstitution in clinical settings.

The EC's approval is based on data from a Phase 2/3 trial conducted in collaboration with the Children's Oncology Group (COG), involving 228 pediatric and adult patients with ALL and LBL who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. The study assessed both IV and IM administration routes and relied on maintaining nadir serum asparaginase activity (NSAA) levels at or above 0.1 U/mL to determine efficacy.

Results showed that for IV administration (25/25/50 mg/m2 MWF), 89.8% of patients maintained NSAA levels ≥ 0.1 U/mL at 48 hours after a dose, while 40% did so at 72 hours post-dose. IM administration (25/25/50 mg/m2 MWF) achieved sustained asparagine activity in 95.9% of patients at 48 hours after a dose and 89.8% at 72 hours post-dose. Other dosing schedules were based on pharmacokinetic and response rate observations.

Regarding safety, the profile of JZP458 was consistent with the reported safety information for ALL/LBL patients receiving asparaginase with combination chemotherapy. Common adverse reactions included anemia, vomiting, thrombocytopenia, neutropenia, and more, with febrile neutropenia, pyrexia, vomiting, and sepsis being the most frequent serious adverse reactions.

The EC's approval extends to all European Union Member States, as well as Iceland, Norway, and Liechtenstein.

For comprehensive information on Enrylaze, including side effects, dosage, contraindications, and precautions, please consult the Summary of Product Characteristics.

Enrylaze (JZP458), also known as Rylaze® in the United States and Canada, is the sole recombinant Erwinia asparaginase derived from a Pseudomonas fluorescens expression platform. It is approved for use in multi-agent chemotherapeutic regimens for ALL and LBL patients who have developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. JZP458 was approved by the U.S. Food and Drug Administration (FDA) in June 2021 and became commercially available in July of the same year in the U.S.

The EC's approval was based on clinical data from a Phase 2/3 study, which included 228 patients with ALL or LBL who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase and had not previously received Erwinia-derived asparaginase. This study aimed to evaluate JZP458's safety, tolerability, and efficacy, measured through serum asparaginase activity (SAA) levels. The study included two parts, one for intramuscular (IM) administration and another to determine the dose and schedule for intravenous (IV) administration.

Acute lymphoblastic leukemia (ALL) is a rapidly progressing cancer of the blood and bone marrow, primarily affecting children. It is the most common childhood malignancy, with 80% of leukemia diagnoses in children attributed to ALL. Survival rates for pediatric patients have improved significantly over the years due to effective multi-agent chemotherapies that incorporate asparaginase. The estimated incidence of ALL and lymphoblastic lymphoma (LBL) in Europe is 1.28 per 100,000, with 59,100 global cases in children in 2017.

Asparaginase is a vital component of multi-agent chemotherapy in ALL, but about 30% of patients develop hypersensitivity to E. coli-derived asparaginase, necessitating treatment discontinuation or a switch to a non-E. coli-derived asparaginase preparation. Patients who do not receive asparaginase due to hypersensitivity or those who do not complete their prescribed doses often experience poor outcomes.

Lymphoblastic lymphoma (LBL) is a rare, aggressive subtype of non-Hodgkin's lymphoma, primarily affecting teenagers and young adults under 35. It represents 25-35% of NHL cases in childhood and adolescence. LBL is characterized by rapid growth and early spread to different body parts.

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