Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) / Jazz, Ligand - LARVOL DELTA

Non-NCPD Lunch Symposium - Hosted by Jazz Pharmaceutical-Rylaze (APHON 2025) - "Sponsored by Jazz Pharmaceutical-Rylaze"

Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) With or Without Rituximab Plus Recombinant Erwinia Asparaginase (JZP458) for the Treatment of Newly Diagnosed Ph Negative B-Acute Lymphoblastic Leukemia or T Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University of Washington | Initiation date: Jun 2025 ➔ Sep 2025

Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

Jazz Pharmaceuticals Announces First Quarter 2025 Financial Results and Updates 2025 Financial Guidance (PRNewswire) - "Key Highlights: Submitted sNDA for Zepzelca in combination with atezolizumab (Tecentriq) as maintenance therapy in 1L ES-SCLC based on the potentially practice-changing results from the Phase 3 IMforte trial. Data from trial to be presented at the 2025 ASCO Annual Meeting in June 2025; Acquisition of Chimerix added dordaviprone to late-stage pipeline, representing near-term commercial opportunity; PDUFA target data of August 18, 2025...Commercial Updates: (i) Rylaze/Enrylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze/Enrylaze net product sales decreased 8% to $94.2 million in 1Q25 compared to 1Q24. This decrease was driven by headwinds from an update to Children's Oncology Group (COG) pediatric treatment protocols for acute lymphoblastic leukemia made in mid-2024 that impacted timing of asparaginase administration."

FDA filing • PDUFA • Sales • Acute Lymphocytic Leukemia • Diffuse Glioma • Small Cell Lung Cancer

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov) - P2 | N=153 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Type I and III Hypersensitivity Reactions to Asparaginase in T-Cell Acute Lymphoblastic Leukemia (ASPHO 2025) - "In Consolidation, she developed tachypnea, vomiting, and rash within 2 minutes of the second calasparage infusion, which improved with intravenous (IV) diphenhydramine and hydrocortisone. Asparaginase hypersensitivity reactions risk both patient safety and inferior outcomes for pediatric leukemia. Our case highlights how even successful management of type I hypersensitivity reactions may not lead to therapeutic drug exposure in a sensitized patient, who remains at risk for other dose-limiting immune-mediated drug reactions. Routine drug level monitoring during therapy both with calaspargase and Rylaze may help detect silent drug inactivation and ascertain risk for developing clinical hypersensitivity."

Acute Lymphocytic Leukemia • Dermatology • Hematological Malignancies • Immunology • Leukemia • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Orthopedics • Pain • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Urticaria

Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2/3 | N=790 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2028 ➔ Sep 2028

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations (clinicaltrials.gov) - P3 | N=1186 | Recruiting | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Hypersensitivity to Recombinant Erwinia Asparaginase (JZP458) in Acute Lymphoblastic Leukemia and Management With Desensitization. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology

Asparaginase Erwinia Chrysanthemi With Chemotherapy for the Treatment of High-Risk Adults With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma (clinicaltrials.gov) - P2 | N=53 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics

Business Updates: Commercial Updates (PRNewswire) - "Rylaze/Enrylaze net product sales increased 4% to $410.8 million in 2024 and were in line in 4Q24 compared to the same periods in 2023 despite headwinds from Children's Oncology Group (COG) protocol changes that impacted timing of asparaginase administration. The temporary impact to Rylaze net product sales due to previously announced COG pediatric acute lymphoblastic leukemia (ALL) protocol updates is still expected to normalize by early 2025....Zepzelca net product sales increased 11% to $320.3 million in 2024 and increased 6% to $78.3 million in 4Q24 compared to the same periods in 2023....Ziihera net product sales were $1.1 million in 2024 and 4Q24 after the initial product launch and availability in December of 2024 following FDA approval in November."

Sales • Acute Lymphocytic Leukemia • Biliary Tract Cancer • Small Cell Lung Cancer

A 12-Step Desensitization Protocol for Calaspargase Pegol-mknl. (PubMed, J Pediatr Pharmacol Ther) - "Asparaginase Erwinia chrysanthemi (recombinant)-rywn (recombinant Erwinia) is an alternative for those with HSRs to pegaspargase. Here, we describe an 11-year-old boy with relapsed ALL who developed HSRs to both pegaspargase and recombinant Erwinia. This is the report of a novel desensitization protocol for calaspargase pegol-mknl (calaspargase) with no adverse events and adequate serum asparaginase activity."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov) - P2 | N=171 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jan 2025 ➔ Apr 2025

Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • KMT2A • MCL1

Ancestral L-Asparaginases Are Cytotoxic Against ALL Cell Lines with Predicted Reduced Immunogenicity (ASH 2024) - "An-104 had impressive killing against these cells with the calculated IC50 in a similar range to that reported of Rylaze®, the recently FDA approved Erwinia L-ASNase...In summary using ASR as a protein discovery and optimization platform, we have generated An-L-ASNase candidates possessing i) comparable ASNase-specific activity, ii) similar cytotoxic activity against ALL cell lines, and iii) lower predicted immunogenicity risk compared to existing commercial ASNase products. Based on these results and ongoing optimization studies, we expect to advance a bio-better next-generation humanized ASNase candidate into clinical development."

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • HLA-DRB1

Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) With or Without Rituximab Plus Recombinant Erwinia Asparaginase (JZP458) for the Treatment of Newly Diagnosed Ph Negative B-Acute Lymphoblastic Leukemia or T Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: University of Washington

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

Jazz Pharmaceuticals Announces Third Quarter 2024 Financial Results (PRNewswire) - "Commercial Updates:...(i) Rylaze/Enrylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze/Enrylaze net product sales were $98.8 million in 3Q24, a decrease of 6% compared to the same period in 2023. There is a temporary impact to Rylaze revenue due to a recent update to pediatric acute lymphoblastic leukemia (ALL) protocols regarding timing of asparaginase administration; (ii) Zepzelca (lurbinectedin): Zepzelca net product sales were $85.8 million in 3Q24, an increase of 10% compared to the same period in 2023."

Sales • Acute Lymphocytic Leukemia • Small Cell Lung Cancer

Recombinant Erwinia Asparaginase (JZP458) in ALL/LBL: Complete Follow-Up of the Children's Oncology Group AALL1931 Study. (PubMed, Blood Adv) - P2/3 | "JZP458 achieves therapeutic NSAA levels via multiple IM and IV dosing schedules based on a combination of observed and modeled data with a safety profile consistent with other asparaginases. Clinicaltrials.gov Identifier: NCT04145531."

Journal • Acute Lymphocytic Leukemia • Allergy • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Pancreatitis

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov) - P2 | N=171 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2027 ➔ Dec 2028 | Initiation date: Oct 2024 ➔ Jan 2025 | Trial primary completion date: Dec 2027 ➔ Dec 2028

Combination therapy • Trial completion date • Trial initiation date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • KMT2A • MCL1

A Study to Determine Number of Patients Who Develop High Ammonia Levels After Receiving Recombinant Erwinia Asparaginase (clinicaltrials.gov) - P=N/A | N=10 | Recruiting | Sponsor: Mayo Clinic

New trial • Hematological Malignancies • Leukemia • Oncology

Hepatic veno-occlusive disease with asparaginase products: a review of cases reported to the FDA adverse event reporting system and published in the literature. (PubMed, Pediatr Hematol Oncol) - "To evaluate this safety concern with asparaginase (i.e. Asparlas, Oncaspar, Rylaze, and Erwinaze) use, we performed a postmarketing review of hepatic VOD reports retrieved from the FDA Adverse Event Reporting System database and literature with these four products. Based on the totality of data, including temporality and biologic plausibility, we determined hepatic VOD to be a class effect with asparaginase products. These data contributed to the addition of hepatic VOD to the hepatoxicity warning in the US Prescribing Information for asparaginase class products."

Adverse events • Journal • Review • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hepatology • Leukemia • Oncology • Pediatrics • Thrombosis

AALL1731: A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=6720 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Active, not recruiting

Combination therapy • Enrollment closed • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology

AALL1731: A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=6720 | Suspended | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2029 ➔ Sep 2027 | Trial primary completion date: Jun 2029 ➔ Sep 2027

Combination therapy • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome (clinicaltrials.gov) - P3 | N=280 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Jun 2024 ➔ Jul 2025

Trial completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • GATA1

AALL1621: Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Children's Oncology Group | Trial completion date: Dec 2024 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Mar 2026

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD22 • KMT2A

RECOMBINANT ERWINIA ASPARAGINASE (JZP458) IN ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOBLASTIC LYMPHOMA (ALL/LBL): POST HOC ANALYSIS OF ADVERSE EVENTS OF INTERESTS FROM AALL1931 (EHA 2024) - P2/3 | "The safety profile of JZP458 is consistent with other asparaginases in patients with ALL/LBL and generally similar across age and ethnicity subgroups."

Adverse events • Retrospective data • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Oncology • Pancreatitis • Pediatrics • Thrombosis

Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL): Post hoc analysis of adverse events of interest from AALL1931. (ASCO 2024) - P2/3 | "The safety profile of JZP458 is consistent with other ASPs in patients with ALL/LBL and generally similar across age and ethnicity subgroups."

Adverse events • Retrospective data • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Oncology • Pancreatitis • Thrombosis