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Trade names | Asparlas |
Other names | EZN-2285, calaspargase pegol-mknl |
AHFS/Drugs.com | Monograph |
MedlinePlus | a619015 |
License data | |
Routes of administration | Intravenous |
Drug class | Antineoplastic agents |
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Calaspargase pegol, sold under the brand name Asparlas, is a medication for the treatment of acute lymphoblastic leukemia (ALL). It is approved in the United States as a component of a multi-agent chemotherapeutic regimen for ALL in pediatric and young adult patients aged one month to 21 years. [5]
Calaspargase pegol is an engineered protein consisting of the E. coli -derived enzyme L-asparaginase II conjugated with succinimidyl carbonate monomethoxypolyethylene glycol (pegol). [6] The L-asparaginase portion hydrolyzes L-asparagine to L-aspartic acid depriving the tumor cell of the L-asparagine it needs for survival. [6] The conjugation with the pegol group increases the half-life of the drug making it longer acting.
The most common (incidence ≥ 10%) grade ≥ 3 adverse reactions are elevated transaminase, increased bilirubin, pancreatitis, and abnormal clotting studies. [5]
In December 2018, calaspargase pegol-mknl was approved in the United States as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age one month to 21 years. [5] [7] [8]
Approval was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity above the level of 0.1 U/mL when using calaspargase pegol-mknl, 2500 U/m2 intravenously, every three weeks. [5] The pharmacokinetics of calaspargase pegol-mknl were studied when administered in combination with multiagent chemotherapy in 124 subjects with B-cell lineage ALL. [5]
The FDA approved calaspargase pegol-mknl based on evidence primarily from two clinical trials (Trial 1/NCT01574274 and Trial 2/AALL07P4) of 237 subjects with acute lymphoblastic leukemia (ALL). [8] The trials were conducted in the United States and Canada. [8]
Trial 1 enrolled subjects 1 to 20 years old who were recently diagnosed with ALL or lymphoblastic lymphoma. [8] Subjects received calaspargase pegol-mknl or pegaspargase (a drug that helps convert asparagine to other substances) as part of a combination of drugs used for treatment of ALL. [8] The trial had 2 phases. [8] Subjects received calaspargase pegol-mknl or pegaspargase intravenously on Day 7 of the first phase. [8] Subjects received either calaspargase pegol-mknl intravenously every 3 weeks for 10 doses or pegaspargase intravenously every 2 weeks for 15 doses during the second phase. [8] The benefit of calaspargase pegol-mknl was assessed by measuring the activity level of asparaginase in the blood on Days 7, 11, 18, 25, and 32 of the first phase and comparing it to pegaspargase. [8]
Trial 2 enrolled subjects 1 to 18 years old who were recently diagnosed with high-risk ALL. [8] Subjects received one of 2 doses of calaspargase pegol-mknl or pegaspargase intravenously as part of a combination of drugs used for treatment. [8] Subjects received calaspargase pegol-mknl or pegaspargase on Day 4 of the first phase and Days 2 and 22 of the second phase. [8] Subjects received up to 12 doses of calaspargase pegol-mknl or pegaspargase intravenously depending on the bone marrow response. [8] The benefit of calaspargase pegol-mknl was assessed by measuring the concentration of drug in the body over 25 days (AUC) and the maximum amount of drug in the blood after a single dose (Cmax). [8] The AUC and Cmax of calaspargase pegol-mknl were compared to pegaspargase. [8]
Calaspargase pegol-mknl received FDA orphan drug designation. [5] The approval was granted to Servier Pharmaceuticals LLC. [5]