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

A phase 2 study evaluating the safety and efficacy of first line asparaginase recombinant erwinia asparaginase (Rylaze) during pediatric-inspired regimen in high-risk adults with newly diagnosed ALL or lbl (ASH 2025) - P2 | "Background and Significance: Pegaspargase-based therapy for acute lymphoblastic leukemia (ALL) offers well-established benefits but treatment-related toxicity precludes its widespread adoption. If our study demonstrates the tolerability and safety of using frontline recombinant Erwinia asparaginase during induction in high-risk adults with ALL, this approach could potentially establish it as the first-line asparaginase in this population and support its use in subsequent treatment cycles. Acknowledgements:This study is financially supported by Jazz Pharmaceuticals, which also conducted a courtesy medical review of this abstract."

Clinical • P2 data • Acute Lymphocytic Leukemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Obesity • Pancreatitis • Pediatrics • Thrombosis

AAML1831: 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 | Trial completion date: Sep 2027 ➔ Jun 2029 | Trial primary completion date: Sep 2027 ➔ Jun 2029

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

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: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2026 ➔ Dec 2026

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

A Single Center, 10-Year Experience of CALGB-10403 Regimen in AYA Population with Philadelphia-Chromosome Negative Acute Lymphoblastic Leukemia (ASH 2023) - "One of the patients with refractory disease underwent further therapy with blinatumomab, inotuzumab, CAR-T and allogeneic stem cell transplantation and is alive at 16 months from diagnosis...Noteworthy adverse effects include neutropenic fever (65%), liver function tests (LFT) abnormalities (70%), and neuropathy from vincristine (70%). Peg-asparaginase administration was associated with pancreatitis in 12%, thromboembolism in 30% and hypersensitivity reactions in 24% requiring switching to alternative forms of asparaginase products (erwinia and Rylaze)... The pediatric-inspired regimen CALGB 10403 was safe and efficacious in our AYA Ph- ALL population with no deaths due to treatment and a 5-year overall survival of 94%. Toxicities, especially from peg-asparaginase, should be closely monitored. While most patients will attain durable remission/cure, the minority with refractory or relapsed disease can still be successfully salvaged to achieve long term survival."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pancreatitis • Pediatrics • T Acute Lymphoblastic Leukemia • Transplantation • KMT2A

Unveiling Putative Pathway Enrichment Following Crisantaspase Treatment in AML through RNA Sequencing Analysis (ASH 2023) - " We utilized Rylaze, an FDA-approved Erwinia crisantaspase, to deplete exogenous Gln. This study represents a significant contribution towards advancing our understanding of amino acid-regulated metabolic pathways in AML, with potential implications for other Gln metabolism-dependent cancers as well."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CHAC1 • S100P

UPDATE AML: UPdated Disease Monitoring And Treatment for Enhanced Outcomes for Pediatric AML (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Joanna Yi | Not yet recruiting ➔ Recruiting

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

Real-World Treatment Patterns Among Patients with Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL) Who Initiated an Asparaginase Treatment after the Approval of Recombinant Erwinia (Rylaze) (ASH 2023) - "Four asparaginase molecules were included in this study, 2 Erwinia-derived - recombinant Erwinia(Rylaze) and native Erwinia (Erwinaze), and 2 E. coli-derived - pegaspargase (Oncaspar) and calaspargase pegol-mknl (Asparlas). Limitations of this study included the nature of the database used, containing mostly outpatient data, and the relatively short study time frame. Future studies with additional data are needed to fully understand the real-world asparaginase use patterns in these patient populations."

Clinical • HEOR • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Chronic Obstructive Pulmonary Disease • Diabetes • Genetic Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Metabolic Disorders • Obesity • Oncology • Pediatrics • Pulmonary Disease • Respiratory Diseases

Immunogenicity of Recombinant Erwinia asparaginase (JZP458) for Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL) (ASH 2023) - P2/3 | "Each dose of E. coli-derived pegaspargase was substituted with 6 doses of JZP458 either intramuscularly (IM, Part A) or intravenously (IV, Part B) on Mon/Wed/Fri over 2 weeks, defined as 1 course. The majority of pts who developed ADAs did not develop HSRs or NAbs. The overall rate of HSRs was similar to literature-reported rates for ASP and appeared to be higher with IV vs IM JZP458. ADA status did not appear to impact PK and other AEs for JZP458."

Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Pediatrics

Efficacy and Safety of Recombinant Erwinia Asparaginase (JZP458) in Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL): Complete Follow-up of the Children's Oncology Group (COG) AALL1931 Study (ASH 2023) - P2/3 | " Eligible patients with ALL/LBL who developed hypersensitivity (grade ≥3 allergic reaction or silent inactivation) to E. coli-derived pegaspargase received JZP458 as part of their multi-agent treatment plan. Results at the completion of AALL1931 in patients with ALL/LBL and allergic reactions or silent inactivation to E. coli-derived asparaginase show the safety profile of JZP458 is consistent with other asparaginases, with no new adverse safety signals. Treatment-related discontinuation rates with IV JZP458 were greater than with IM, primarily due to increased incidence of hypersensitivity/infusion-related reactions along with nausea and vomiting; however, the study was not statistically powered to compare different dosing cohorts. Observed and PPK modeling data demonstrate JZP458 achieves therapeutic NSAA levels via multiple IM and IV dosing schedules, with IM dosing having more sustained SAA, and therefore providing flexibility to patients and physicians."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Lymphoma • Pancreatitis • Pediatrics

A Real-World, Single Institution, Post-Market Comparison of Pegaspargase and Calasparagase Pegol-Mknl Therapeutic Drug Monitoring and Toxicity (ASH 2023) - "Introduction: Calaspargase pegol-mknl (CalPEG) was FDA-approved in December 2018 as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia/lymphoma (ALL/LLy) in pediatric patients and adolescent and young adults (AYA)...Patients received either PEGasp, CalPEG, and/or asparaginase Erwinia chrysanthemi recombinant (Rylaze) and had correlative SAA documented by a validated assay (NEXT Molecular Analytics; Chester, VA)... To our knowledge this is the first single-institution post-market retrospective quality and safety analysis comparing CalPEG and PEGasp therapeutic drug monitoring and toxicity. Interestingly, the incidence of pancreatitis and VTE is significantly higher in patients receiving CalPEG and disproportionately higher in T-lineage. Median peak SAA levels were not predictive of toxicity, though GLM may help provide a predictive model."

Clinical • P4 data • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lymphoma • Oncology • Pancreatitis • Pediatrics • T Acute Lymphoblastic Leukemia • Venous Thromboembolism

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

Business Updates:…Rylaze/Enrylaze (asparaginase erwiniachrysanthemi (recombinant)-rywn) (PRNewswire) - "Net product sales increased 1% to $99.9 million in 3Q25 compared to 3Q24."

Sales • Acute Lymphocytic Leukemia • Lymphoblastic Lymphoma

RISK FACTORS ASSOCIATED WITH HYPOGLYCEMIA DURING ASPARAGINASE THERAPY AND STRATEGIES FOR MANAGEMENT IN PEDIATRIC PATIENTS WITH LEUKEMIA (SIOP 2025) - " Ninety-four patients received calaspargase pegol (CAL-PEG) or recombinant Erwinia asparaginase, with 19 individuals experiencing at least one episode of AAH...Of these 12 patients, 83.3% had not yet received mercaptopurine, a known risk factor for hypoglycemia... Incidence of AAH was 20% among our cohort with most episodes presenting early in therapy after one dose of CAL-PEG. Identifying patients at an increased risk for AAH allows for enhanced glucose monitoring, aiming to reduce severe hypoglycemic events and hospitalizations in this population."

Clinical • Acute Lymphocytic Leukemia • Diabetes • Genetic Disorders • Hematological Malignancies • Hypoglycemia • Leukemia • Obesity • Pediatrics

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 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2028 ➔ Mar 2029 | Trial primary completion date: Apr 2028 ➔ Mar 2029

Enrollment open • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics

An Open-Label, Multicenter Study of RC-P in Patients with Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL) Following Hypersensitivity to E. coli-derived Asparaginases (clinicaltrialsregister.eu) - P2/3 | N=228 | Sponsor: Jazz Pharmaceuticals

New P2/3 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology

Non-NCPD Lunch Symposium: Emily’s Story: A patient’s journey with acute lymphoblastic leukemia (ALL) and Rylaze Treatment (APHON 2025) - "Sponsored by Jazz Pharmaceuticals"

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Recombinant Erwinia Asparaginase and Venetoclax in Combination With Blinatumomab for the Treatment of Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P1 | N=26 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

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: Sep 2025 ➔ Dec 2025

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

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 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Leukemia • Oncology

Jazz Pharmaceuticals Announces Second Quarter 2025 Financial Results and Updates 2025 Financial Guidance (PRNewswire) - "Commercial Updates:...(i) Rylaze/Enrylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn): Rylaze/Enrylaze net product sales decreased 7% to $100.7 million in 2Q25 compared to 2Q24; (ii) Ziihera (zanidatamab-hrii): Ziihera net product sales were $6.0 million in 2Q25 following product launch in December 2024."

Sales • Acute Lymphocytic Leukemia • Biliary Tract Cancer

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: Jul 2025 ➔ Jun 2026

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

UPDATE AML: UPdated Disease Monitoring And Treatment for Enhanced Outcomes for Pediatric AML (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Joanna Yi

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

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