Английская Википедия:Calaspargase pegol
Шаблон:Short description Шаблон:Use dmy dates Шаблон:Infobox drug
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.[1]
Calaspargase pegol is an engineered protein consisting of the E. coli-derived enzyme L-asparaginase II conjugated with succinimidyl carbonate monomethoxypolyethylene glycol (pegol).[2] The L-asparaginase portion hydrolyzes L-asparagine to L-aspartic acid depriving the tumor cell of the L-asparagine it needs for survival.[2] 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.[1]
History
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.[1][3][4]
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.[1] The pharmacokinetics of calaspargase pegol-mknl were studied when administered in combination with multiagent chemotherapy in 124 subjects with B-cell lineage ALL.[1]
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).[4] The trials were conducted in the United States and Canada.[4]
Trial 1 enrolled subjects 1 to 20 years old who were recently diagnosed with ALL or lymphoblastic lymphoma.[4] 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.[4] The trial had 2 phases.[4] Subjects received calaspargase pegol-mknl or pegaspargase intravenously on Day 7 of the first phase.[4] 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.[4] 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.[4]
Trial 2 enrolled subjects 1 to 18 years old who were recently diagnosed with high-risk ALL.[4] Subjects received one of 2 doses of calaspargase pegol-mknl or pegaspargase intravenously as part of a combination of drugs used for treatment.[4] Subjects received calaspargase pegol-mknl or pegaspargase on Day 4 of the first phase and Days 2 and 22 of the second phase.[4] Subjects received up to 12 doses of calaspargase pegol-mknl or pegaspargase intravenously depending on the bone marrow response.[4] 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).[4] The AUC and Cmax of calaspargase pegol-mknl were compared to pegaspargase.[4]
Calaspargase pegol-mknl received FDA orphan drug designation.[1] The approval was granted to Servier Pharmaceuticals LLC.[1]
References
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