Pegaspargase

From discovery to approval

1. 1978 · Earliest report found

   A 1978 paper by Ashihara and colleagues is titled as describing modification of E. coli L-asparaginase with polyethylene glycol (PEG; title only). In 1981 the PEG adduct was given to four patients with chemotherapy-refractory cancers, and a 1984 report by Abuchowski and colleagues described PEG-asparaginase conjugates in mice.^{[2][3][4][5][1]}

2. 1994-02-01 · FDA regular

   As a component of a multi-agent chemotherapeutic regimen for the treatment of pediatric and adult patients with ALL and hypersensitivity to native forms of L-asparaginase^[6]

3. 2006-07-24 · FDA regular

   Supplement expanding the indication to use as a component of a multi-agent first-line chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL)^[7]

4. 2016-01-14 · EMA regular

   Marketing authorisation issued 14 January 2016 (EPAR page; holder Les Laboratoires Servier); as a component of antineoplastic combination therapy in acute lymphoblastic leukaemia in paediatric patients from birth to 18 years and in adults. No conditional, exceptional or accelerated wording was found, so 'regular' is an inference. The page gives no separate European Commission decision date.^[8]

How it works

As for native asparaginase: it removes asparagine from the blood. The label says it is thought to kill leukaemic cells that have low asparagine synthetase and so depend on outside asparagine.^[1]

Where it came from and why

The 1984 report says the conjugates stayed active and stable, with no significant immune response and greatly extended half-lives in mice. A 1993 review names allergic reactions as the main side effect limiting asparaginase, and says PEG greatly decreases the chance of antibodies and prolongs the half-life.

Cancers

• Acute lymphoblastic leukaemia

  The 2024 US label lists first-line treatment of paediatric and adult acute lymphoblastic leukaemia in a multi-agent regimen, and use in patients with hypersensitivity to native forms of L-asparaginase.^[1]

• Refractory haematological malignancy (phase I/II)

  A phase I/II study at MD Anderson treated 37 heavily pretreated patients with refractory haematological malignancy, 19 of them with acute lymphoblastic leukaemia, at 250 to 8000 IU/m2.^[5]

Family and partners

Derived from: Asparaginase (E. coli)

Drugs derived from it: Calaspargase pegol

Worth knowing

• In a clinical pharmacology study of 27 pharmacokinetically evaluable patients, the mean half-life of PEG-L-asparaginase was 357 hours (standard deviation 243), against about 20 hours for the unconjugated enzyme.^[9]
• An FDA staff approval summary of the 2006 first-line approval describes an open-label randomised trial in 118 children aged 1 to 9 years with untreated standard-risk acute lymphoblastic leukaemia: antibodies to asparaginase were found in 7 of 56 (12%) pegaspargase-treated and 16 of 57 (28%) native-enzyme-treated children tested.^[10]
• The same FDA staff approval summary states that pegaspargase was first approved in February 1994 for patients with acute lymphoblastic leukaemia who were hypersensitive to native forms of L-asparaginase.^[10]
• A 2023 review says pharmacokinetic and pharmacodynamic studies of PEG-asparaginase began in the 1980s and were usually done in patients with hypersensitivity to native E. coli asparaginase.^[11]

References

1. U.S. Food and Drug Administration. Oncaspar (pegaspargase) prescribing information, BLA 103411, supplement 5207 approved 13 March 2024 (the label states it may not be the latest approved). Source
2. Ashihara Y, Kono T, Yamazaki S, Inada Y. Modification of E. coli L-asparaginase with polyethylene glycol: disappearance of binding ability to anti-asparaginase serum. Biochem Biophys Res Commun. 1978;83(2):385-91. PubMedDOI
3. Park YK, Abuchowski A, Davis S, Davis F. Pharmacology of Escherichia coli-L-asparaginase polyethylene glycol adduct. Anticancer Res. 1981;1(6):373-6. PubMed
4. Abuchowski A, Kazo GM, Verhoest CR Jr, Van Es T, Kafkewitz D, Nucci ML, et al. Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates. Cancer Biochem Biophys. 1984;7(2):175-86. PubMed
5. Keating MJ, Holmes R, Lerner S, Ho DH. L-asparaginase and PEG asparaginase--past, present, and future. Leuk Lymphoma. 1993;10 Suppl:153-7. PubMedDOI
6. U.S. Food and Drug Administration, Oncology Center of Excellence. Pediatric Oncology Drug Approvals (table current as of February 2026; page content current as of 03/03/2026). Accessed 2026-10-20. Source
7. U.S. Food and Drug Administration. Approval letter, STN BL 103411/5052, pegaspargase (Oncaspar), supplement expanding the indication to first-line multi-agent treatment of acute lymphoblastic leukemia, 2006. Source
8. European Medicines Agency. Oncaspar (pegaspargase): European public assessment report (EPAR) page; marketing authorisation issued 14/01/2016. Page read 2026-10-29. Source
9. Ho DH, Brown NS, Yen A, Holmes R, Keating M, Abuchowski A, et al. Clinical pharmacology of polyethylene glycol-L-asparaginase. Drug Metab Dispos. 1986;14(3):349-52. PubMed
10. Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007;12(8):991-8. PubMedDOI
11. Tong WH, Rizzari C. Back to the future: the amazing journey of the therapeutic anti-leukemia enzyme asparaginase Erwinia chrysanthemi. Haematologica. 2023;108(10):2606-2615. PubMedDOI
12. U.S. Food and Drug Administration. Drugs@FDA: approval date(s) and history, letters, labels for BLA 103411 (Oncaspar, pegaspargase). Page read 2026-10-29. Source