FDA Approves New Enzyme Product for ALL

Roxanne Nelson, RN, BSN

Disclosures

December 21, 2018

The US Food and Drug Administration (FDA) has approved a new drug for the treatment of acute lymphoblastic leukemia (ALL), a cancer of the blood and bone marrow.

The agency has granted approval for calaspargase pegol-mknl (Asparlas, Servier Pharmaceuticals), an asparagine-specific enzyme, to be used as part of a multi-agent chemotherapeutic regimen in pediatric and young adult patients (age 1 month to 21 years). This new product differs from other available pegaspargase products, such as pegaspargase (Oncaspar, Sigma-Tau Pharmaceuticals) and asparaginase (Erwinaze, Jazz Pharmaceuticals), in that it provides for a longer interval between doses. It also has an extended shelf-life beyond that of the current pegylated asparaginase treatment, which helps ensure availability to patients.

Calaspargase contains an asparagine-specific enzyme derived from Escherichia coli and depletes plasma asparagine, selectively killing leukemic cells that are unable to synthesize asparagine because of a lack of asparagine synthetase. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize L-asparagine, and therefore depend on an exogenous source of L-asparagine for survival.

The approval was based on demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using a dose of 2500 U/m2 given intravenously every 3 weeks. The pharmacokinetics were studied in a cohort of 124 patients with B cell lineage ALL who were a median age of 11.5 years (range, 1-26). Within this group, 62 (50%) were male, 102 (82%) white, six (5%) Asian, five (4%) Black or African American, two (2%) Native Hawaiian or Pacific Islander, and nine (7%) other or unknown.

When calaspargase was administered with multi-agent chemotherapy, the results showed that 123 of the 124 patients (99%, 95% CI, 96 - 100) maintained NSAA > 0.1 U/mL at weeks 6, 12, 18, 24, and 30.

The recommended dosage is 2500 units/m2 intravenously administered no more frequently than every 21 days.

The most common (incidence ≥ 10%) grade ≥ 3 adverse reactions associated with this agent were elevated transaminase, increased bilirubin, pancreatitis, and abnormal clotting studies. In a randomized trial, the safety profile of calaspargase pegol-mknl administered every 3 weeks was similar to that of pegaspargase administered every 2 weeks, according to the FDA.

Calaspargase pegol-mknl has received FDA orphan drug designation.

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