Calaspargase pegol

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Calaspargase pegol
Names
Trade namesAsparlas
Other namesCalaspargase pegol-mknl, EZN-2285
Clinical data
Drug classAntineoplastic agents
Main usesAcute lymphoblastic leukemia (ALL)[1]
Side effectsLiver problems, pancreatitis, abnormal blood clotting[1]
Pregnancy
category
  • US: N (Not classified yet)[2]
Routes of
use
Intravenous
External links
AHFS/Drugs.comMonograph
US NLMCalaspargase pegol
MedlinePlusa619015
Legal
License data
Legal status

Calaspargase pegol, sold under the brand name Asparlas, is a medication used to treat acute lymphoblastic leukemia (ALL).[1] It is used with other medications in those aged 1 month to 21 years.[1] It is given by injection into a vein.[3]

Common side effects include liver problems, pancreatitis, and abnormal blood clotting.[1] Other side effects may include allergic reactions, blood clots, and bleeding.[1] Use in pregnancy may harm the baby.[3] It is made by attaching asparaginase to monomethoxy polyethylene glycol (mPEG).[3]

Calaspargase pegol was approved for medical use in the United States in 2018.[1] In the United States a 3,750 unit vial costs about 25,400 USD as of 2021.[4] It is partly made by E. coli.[5]

Medical uses

Dosage

It is given at a dose of 2,500 units/m2 up to once every 3 weeks.[1]

Mechanism of action

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.

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.[7][8][9]

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.[7] The pharmacokinetics of calaspargase pegol-mknl were studied when administered in combination with multiagent chemotherapy in 124 subjects with B-cell lineage ALL.[7]

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).[9] The trials were conducted in the United States and Canada.[9]

Trial 1 enrolled subjects 1 to 20 years old who were recently diagnosed with ALL or lymphoblastic lymphoma.[9] 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.[9] The trial had 2 phases.[9] Subjects received calaspargase pegol-mknl or pegaspagase intravenously on Day 7 of the first phase.[9] 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.[9] The benefit of calaspargase pegol-mknl was assessed by measuring the activity level of asparginase in the blood on Days 7, 11, 18, 25, and 32 of the first phase and comparing it to pegaspargase.[9]

Trial 2 enrolled subjects 1 to 18 years old who were recently diagnosed with high-risk ALL.[9] Subjects received one of 2 doses of calaspargase pegol-mknl or pegaspargase intravenously as part of a combination of drugs used for treatment.[9] Subjects received calaspargase pegol-mknl or pegaspargase on Day 4 of the first phase and Days 2 and 22 of the second phase.[9] Subjects received up to 12 doses of calaspargase pegol-mknl or pegaspargase intravenously depending on the bone marrow response.[9] 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).[9] The AUC and Cmax of calaspargase pegol-mknl were compared to pegaspargase.[9]

Calaspargase pegol-mknl received FDA orphan drug designation.[7] The approval was granted to Servier Pharmaceuticals LLC.[7]

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "DailyMed - ASPARLAS- calaspargase pegol injection, solution". dailymed.nlm.nih.gov. Archived from the original on 31 October 2021. Retrieved 29 December 2021.
  2. "Calaspargase pegol (Asparlas) Use During Pregnancy". Drugs.com. 29 October 2019. Archived from the original on 30 November 2020. Retrieved 23 January 2020.
  3. 3.0 3.1 3.2 "Calaspargase Pegol-mknl". drugs.com. American Society of Health-System Pharmacists. Retrieved 29 December 2021.
  4. "Asparlas Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 19 April 2021. Retrieved 29 December 2021.
  5. "calaspargase pegol-mknl". www.cancer.gov. 2 February 2011. Archived from the original on 17 January 2021. Retrieved 29 December 2021.
  6. 6.0 6.1 "Calaspargase pegol-mknl". NCI Drug Dictionary. National Cancer Institute. Archived from the original on 13 October 2020. Retrieved 16 September 2021.
  7. 7.0 7.1 7.2 7.3 7.4 "FDA approves longer-acting calaspargase pegol-mknl for ALL" (Press release). U.S. Food and Drug Administration (FDA). 20 December 2018. Archived from the original on 24 January 2020. Retrieved 23 January 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  8. "Drug Approval Package: Asparlas". U.S. Food and Drug Administration (FDA). 22 January 2019. Archived from the original on 24 January 2020. Retrieved 23 January 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  9. 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 "Drug Trials Snapshots: Asparlas". U.S. Food and Drug Administration (FDA). 20 December 2018. Archived from the original on 24 January 2020. Retrieved 23 January 2020. Public Domain This article incorporates text from this source, which is in the public domain.

External links

Identifiers: