General Information

Rylaze (asparaginase erwinia chrysanthemi (recombinant)- rywn) is an asparagine specific enzyme.

Rylaze is specifically indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase.

Rylaze is supplied as an injection for intravenous administration. When replacing a long-acting asparaginase product, the recommended dosage is 25 mg/m2 administered intramuscularly every 48 hours. 

Mechanism of Action

Rylaze (asparaginase erwinia chrysanthemi (recombinant)- rywn) is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect of Rylaze is based on the killing of leukemic cells due to depletion of plasma asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival.

Side Effects

Adverse effects associated with the use of Rylaze may include, but are not limited to, the following:

• abnormal liver test
• nausea
• musculoskeletal pain
• fatigue
• infection
• headache
• pyrexia
• drug hypersensitivity
• febrile neutropenia
• decreased appetite
• stomatitis
• bleeding
• hyperglycemia

Clinical Trial Results

The FDA approval was based on data from an ongoing pivotal Phase 2/3 single-arm, open-label, multicenter, dose confirmation study evaluating pediatric and adult patients with ALL or LBL who have had an allergic reaction to E. coli-derived asparaginases and have not previously received asparaginase erwinia chrysanthemi. The study is being conducted in two parts. The first part is investigating the intramuscular (IM) route of administration, including a Monday-Wednesday-Friday dosing schedule. The second part remains active to further confirm the dose and schedule for the intravenous (IV) route of administration. The determination of efficacy was measured by serum asparaginase activity (SAA) levels.

The FDA used data from the first of three IM cohorts as the basis for approval. The data demonstrated the achievement and maintenance of nadir serum asparaginase activity (NSAA) greater than or equal to the level of 0.1 U/mL at 48 hours using IM doses of Rylaze 25 mg/m². The results of modeling and simulations showed that for a dosage of 25 mg/m² administered intramuscularly every 48 hours, the proportion of patients maintaining NSAA ≥ 0.1 U/mL at 48 hours after a dose of Rylaze was 93.6%.