Regulatory Decision Summary for Oncaspar

The pivotal study CCG-1962 that evaluated the use of Oncaspar in the first-line treatment of ALL (aged 1 to 9 years of age) demonstrated that asparagine depletion was similar between the Oncaspar and native E. Coli L-asparaginase (ASNase) arms during all three phases of treatment. The 3-year EFS rate was 83% in the Oncaspar arm and 79% in the native ASNase arm. Two supportive studies conducted in newly diagnosed ALL patients (AALL07P4 and DFCI 05-001) further support the benefit of Oncaspar in pediatric and adult ALL.

In addition, a systemic literature review including a series of clinical trials (including both pediatric and adult patients) completed over several years provided the foundation that Oncaspar is an acceptable component of the standard of care for ALL patients. Oncaspar has been marketed in other jurisdictions (for example [e.g.], United States and Eurpean Union), and is commonly used as a standard of care for the treatment of ALL patients in Canada.

One compelling benefit of Oncaspar is its dosing advantage over native ASNase. Because of the significant longer half-life of Oncaspar, fewer injections are required.

The most important safety findings associated with Oncaspar were anaphylaxis and allergic reactions/hypersensitivity, thrombosis, coagulopathy, hepatotoxicity/abnormal liver function (e.g., hyperbilirubinemia, hyperlipidemia and elevated transaminases), pancreatitis, hematological disorders, central nervous system (CNS) toxicity (e.g., CNS thrombosis and peripheral neuropathy), infections (e.g., sepsis), and glucose intolerance. Other toxicities observed with Oncaspar were hyperglycemia, febrile neutropenia, gastrointestinal disorders (e.g., abdominal pain), hypoxia and pain in extremities. The overall safety profile of Oncaspar appears to be consistent with the known safety profile of native ASNase and is consistent with the experience of Oncaspar in clinical trials and in the post-market setting.

Overall, ALL patients treated with Oncaspar showed similar asparagine depletion to that seen with native ASNase without any evidence of decrease in EFS. Oncaspar also allows for less frequent dosing, and good tolerance with an acceptable and manageable toxicity profile. Based on the totality of evidence from clinical data, systemic literature review, post-market experience, and current use of Oncaspar in clinical practice, the overall risk benefit profile of Oncaspar is considered favourable for the treatment of patients with ALL.