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Asparaginase Erwinia chrysanthemi (crisantaspase)

Also known as Erwinaze, Rylaze, Enrylaze, JZP-458

An asparagine-depleting enzyme from Erwinia chrysanthemi that does not cross-react immunologically with E. coli enzymes. Used for leukaemia and lymphoblastic lymphoma after hypersensitivity to E. coli asparaginase; now also made by recombinant technology.

From discovery to approval

  1. c. 1970 · Earliest report found

    A 2023 review dates the start of Erwinia chrysanthemi asparaginase's clinical journey to the 1970s, when it was found to have pharmacokinetics similar to native E. coli asparaginase but a shorter half-life. It was first used first-line and later became the preferred second-line product. No dated first paper was found.[2][3][4][1]

  2. 2011-11-18 · FDA regular

    BLA 125359: as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukaemia in patients who have developed hypersensitivity to E. coli-derived asparaginase. The letter read is a replacement letter whose effective action date stays 18 November 2011. No conditional, exceptional or accelerated wording was found, so 'regular' is an inference.[5]

  3. 2021-06-30 · FDA regular

    Original approval of BLA 761179 (letter signed 30 June 2021; Drugs@FDA lists 06/30/2021, orphan): as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukaemia and lymphoblastic lymphoma in adult and paediatric patients 1 month or older who have developed hypersensitivity to E. coli-derived asparaginase. No conditional, exceptional or accelerated wording was found, so 'regular' is an inference.[6]

  4. 2023-09-15 · EMA regular

    Marketing authorisation issued 15 September 2023 (EPAR page): as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukaemia and lymphoblastic lymphoma in adults and paediatric patients (1 month and older) who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. No conditional, exceptional or accelerated wording was found, so 'regular' is an inference.[7]

How it works

Converts asparagine to aspartic acid and ammonia. The Rylaze label says the effect is based on killing leukaemic cells with low asparagine synthetase, which depend on outside asparagine.[1]

Where it came from and why

Hypersensitivity and silent inactivation are reported in up to 60-70% of patients given E. coli-derived products, and Erwinia asparaginase is a non-cross-reactive option. Recurring shortages led to a recombinant version with the same amino acid sequence, made in Pseudomonas fluorescens.

Cancers

Worth knowing

  • A 2023 review states that the glutaminase activity of Erwinia asparaginase is approximately five times higher than that of E. coli asparaginase products.[2]
  • A 2023 review says the 2021 FDA approval of the recombinant product rested on interim results of Children's Oncology Group study AALL1931, and that supply shortages of the non-recombinant product over the last two decades prompted its development.[2]
  • In the complete follow-up of AALL1931, 51 patients in intramuscular cohort 1c (25/25/50 mg/m2 on a Monday, Wednesday, Friday schedule) were evaluated; the proportion maintaining nadir serum asparaginase activity of at least 0.1 IU/mL at the last 72 hours of course 1 was 90% (95% CI 81-98).[8]

References

  1. U.S. Food and Drug Administration. Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) prescribing information, BLA 761179, supplement 7 approved 15 April 2024 (the label states it may not be the latest approved). Source
  2. 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
  3. Maese L, Rizzari C, Coleman R, Power A, van der Sluis I, Rau RE. Can recombinant technology address asparaginase Erwinia chrysanthemi shortages?. Pediatr Blood Cancer. 2021;68(10):e29169. PubMedDOI
  4. Gao C, Ma X, Zhang Z, Lu Q, Ashby CR Jr, Wei L, et al. Asparaginase Erwinia chrysanthemi for acute lymphoblastic leukemia and lymphoblastic lymphoma. Drugs Today (Barc). 2022;58(6):261-271. PubMedDOI
  5. U.S. Food and Drug Administration. Replacement approval letter, BL 125359/0 (Erwinaze, asparaginase Erwinia chrysanthemi), EUSA Pharma (USA); the effective date of the action remains 18 November 2011. Source
  6. U.S. Food and Drug Administration. Approval letter, BLA 761179 (Rylaze, asparaginase erwinia chrysanthemi (recombinant)-rywn), Jazz Pharmaceuticals Ireland, 2021. Source
  7. European Medicines Agency. Enrylaze (asparaginase erwinia chrysanthemi, recombinant): European public assessment report (EPAR) page; marketing authorisation issued 15/09/2023. Page read 2026-10-29. Source
  8. Maese L, Loh ML, Choi MR, Agarwal S, Aoki E, Liang Y, et al. Recombinant Erwinia asparaginase (JZP458) in ALL/LBL: complete follow-up of the Children's Oncology Group AALL1931 study. Blood Adv. 2025;9(1):66-77. PubMedDOI
  9. U.S. Food and Drug Administration. Erwinaze (asparaginase Erwinia chrysanthemi) prescribing information, BLA 125359, initial U.S. approval 2011. Source
  10. U.S. Food and Drug Administration. Drugs@FDA: approval date(s) and history, letters, labels for BLA 761179 (Rylaze, asparaginase erwinia chrysanthemi (recombinant)-rywn). Page read 2026-10-29. Source