Pegaspargase (Oncaspar®): A Comprehensive Monograph on its Biochemistry, Pharmacology, and Clinical Application in Acute Lymphoblastic Leukemia

Introduction and Overview

Pegaspargase is a cornerstone of modern antineoplastic therapy for Acute Lymphoblastic Leukemia (ALL), representing a significant advancement in the application of enzyme-based therapeutics in oncology.[1] As a biotechnological drug, specifically a modified protein therapy, Pegaspargase leverages a unique metabolic vulnerability inherent to malignant lymphoblasts, thereby providing a targeted mechanism of cytotoxicity.[1] This comprehensive report details the drug's intricate biochemical structure, its unique pharmacological profile, extensive clinical applications and efficacy, a thorough safety and risk management profile, and its notable regulatory and commercial history.

The development of Pegaspargase was a direct and highly successful response to the significant clinical limitations of its predecessor, native L-asparaginase derived from Escherichia coli.[1] While effective, native L-asparaginase was hampered by two primary drawbacks: a high incidence of immunogenic responses, including severe hypersensitivity and anaphylaxis, and a short plasma half-life that necessitated frequent and often painful intramuscular injections to maintain therapeutic enzyme activity.[1] These challenges frequently led to treatment interruptions, dose reductions, and a substantial treatment burden for patients, particularly in pediatric populations.