In short
Recombinant L-asparaginase is a protein-based enzyme medicine used as part of combination chemotherapy for acute lymphoblastic leukemia (ALL). It is authorised in the EU as Enrylaze and is being studied in two clinical trials: a Phase 2 trial in 86 adults with relapsed or refractory T-cell ALL, and a Phase 3 trial in 3,150 children and adolescents with newly diagnosed ALL.
Recombinant L-asparaginase is a protein-based enzyme medicine used as part of combination chemotherapy for acute lymphoblastic leukemia (ALL). It appears in the EU Clinical Trials Information System under the product name Enrylaze 10 mg/0.5 mL, solution for injection/infusion, and is authorised as a medicine in the EU.
Key points
- Recombinant L-asparaginase is authorised in the EU as Enrylaze for intravenous use.
- It is being tested in a Phase 2 trial for relapsed or refractory T-cell ALL in 86 participants.
- A large Phase 3 trial is studying it in 3,150 children and adolescents with ALL.
- The Phase 2 trial measures hematological remission rate within 3 months of randomisation.
- The substance is classified as asparaginase (ATC code L01XX02).
- Known serious side effects include pancreatitis, thrombosis, and hepatotoxicity.
What is recombinant L-asparaginase?
Recombinant L-asparaginase is an enzyme classified as asparaginase (ATC code L01XX02) in the group of antineoplastic agents. It is a protein-based substance produced by recombinant technology. The product name under which it appears in the registry is Enrylaze 10 mg/0.5 mL, solution for injection/infusion, and the marketing authorisation holder is Jazz Pharmaceuticals Ireland Ltd. The substance is authorised as a medicine in the EU.
A related pegylated form of L-asparaginase, calaspargase pegol-mknl (Asparlas), is approved in the United States for the treatment of ALL in pediatric and young adult patients aged 1 month to 21 years.
How does recombinant L-asparaginase work?
L-asparaginase is an asparagine-specific enzyme. It breaks down the amino acid asparagine in the blood. Leukemia cells, unlike normal cells, cannot make their own asparagine and depend on taking it from the blood. When asparagine is depleted, the leukemia cells cannot survive. Recombinant L-asparaginase 1 from Saccharomyces cerevisiae has been described as an allosteric enzyme with antineoplastic activity.
Which conditions is recombinant L-asparaginase used or studied for?
- Relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) — a form of leukemia that has returned after treatment or did not respond to previous treatment, being studied in a Phase 2 trial.
- Acute lymphoblastic leukemia in children and adolescents — newly diagnosed ALL in young patients, being studied in a Phase 3 international treatment protocol.
- Acute lymphoblastic leukemia in pediatric and young adult patients — the approved indication for the related pegylated form calaspargase pegol-mknl in the United States, for patients aged 1 month to 21 years.
How is recombinant L-asparaginase given?
In the registry records, recombinant L-asparaginase is formulated as a solution for injection/infusion and is given by intravenous administration. In the Phase 2 trial, Enrylaze is given at a dose of 25 mg/m² intravenously. In the Phase 3 trial, Enrylaze is given at a dose of 50 mg/m² intravenously. The related pegylated product Asparlas is given intravenously at a dose of 2,500 units/m² no more frequently than every 21 days.
What do the clinical trials show?
Two clinical trials involving recombinant L-asparaginase are registered. The substance is the test medicine in one trial and appears in the intervention list of a second trial.
Which conditions are being studied?
One Phase 2 trial studies recombinant L-asparaginase in adults with relapsed or refractory T-cell acute lymphoblastic leukemia. It is a precision medicine randomised trial that assigns patients to targeted treatment combinations based on a functional approach. A second, much larger Phase 3 trial studies the substance as part of an international collaborative treatment protocol for children and adolescents with newly diagnosed acute lymphoblastic leukemia.
What phases and status do the trials have?
The Phase 2 trial (2024-516570-30-00) is authorised and plans to enrol 86 participants. The Phase 3 trial (2025-522190-11-01) is authorised and plans to enrol 3,150 participants. Both trials are interventional studies.
What are the trials measuring?
The Phase 2 trial measures hematological remission rate, a composite outcome defined as the best response observed within 3 months after randomisation — either complete remission or remission without complete hematological recovery. The Phase 3 trial measures disease-free survival time, defined as the time from randomisation until relapse, second malignancy, or death from any cause.
Who can take part in these trials?
The Phase 2 trial enrols patients with relapsed or refractory T-cell acute lymphoblastic leukemia. The Phase 3 trial enrols children and adolescents with acute lymphoblastic leukemia.
What side effects are known?
For the related pegylated L-asparaginase product Asparlas, the most common grade 3 or higher adverse reactions, occurring in at least 10% of patients, were elevated transaminase, increased bilirubin, pancreatitis, and abnormal clotting studies. Serious side effects reported with L-asparaginase therapy include hypersensitivity reactions, pancreatitis, thrombosis, hemorrhage, and hepatotoxicity including hepatic veno-occlusive disease.