Jazz Pharmaceuticals Presents Positive Data from Phase 2/3 Trial of Rylaze® (asparaginase erwinia chrysanthemi (recombinant)-rywn) in Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma at the ASCO 2022 Annual Meeting
Oral presentation confirms patients achieved clinically meaningful nadir serum asparaginase activity throughout the course of Rylaze treatment with intramuscular dosing regimen administered 25/25/50 mg/m2 on Monday/Wednesday/Friday
These results confirm the interim trial analysis presented in
"We are excited to share these results from the Phase 2/3 trial of Rylaze highlighting the clinically meaningful nadir serum asparaginase activity from the Monday/Wednesday/Friday dosing regimen, which supports a new dosing schedule that aligns with current clinical practice," said
"Asparaginase-based therapies remain a cornerstone in ALL and LBL treatment, and Rylaze has been an important option for patients who develop a hypersensitivity to an E. coli-derived asparaginase since its approval last year," said trial primary investigator Dr. Luke Maese, associate professor of pediatric hematology-oncology at the University of Utah, Primary Children's Hospital and Huntsman Cancer Institute. "It's encouraging to see these data further support an IM Monday/Wednesday/Friday dosing schedule for Rylaze, which is more in line with clinical practice in the
Rylaze was approved in the
Data presented at ASCO include efficacy and safety results from the Phase 2/3 open-label, multicenter, pharmacokenitic (PK) trial of Rylaze (also known as JZP458) in patients with ALL/LBL who developed hypersensitivity or silent inactivation to a long-acting E. coli-derived asparaginase. These results are from Part A of the trial, which investigated three cohorts via IM administration:
- Cohort 1a (n=33): studied a dose of 25 mg/m2 Monday/Wednesday/Friday
- Cohort 1b (n=83): studied a dose of 37.5 mg/m2 Monday/Wednesday/Friday
- Cohort 1c (n=51): studied a dose of 25 mg/m2 on Monday and Wednesday and 50 mg/m2 on Friday
The primary efficacy endpoint of the trial was the proportion of patients with NSAA levels ≥0.1 IU/mL at the last 72-hours during the first treatment course.
The key secondary endpoint was the proportion of patients with NSAA levels ≥0.1 IU/mL at the last 48-hours during the first treatment course.
A population PK (PPK) model was developed based on SAA data from the clinical trial to characterize the PK of JZP458 when given IM and to inform dosing decisions. Simulated data from the PPK model matched the observed data well.
Based on a PPK modeling and simulation analysis, the proportion of patients predicted to achieve NSAA levels ≥0.1 IU/mL with a 95% CI in Cohort 1c at the last 72- and 48-hour in Course 1 were 92% (91%, 93%) and 94% (93%, 95%) respectively, based on modeled data.
In Cohort 1c in this trial, the following treatment-related adverse events (TRAEs) leading to discontinuation were observed:
Patients, n (%)
25/25/50 mg/m2 MWF
(n = 51)
Any TRAE leading to study drug discontinuation
There were no TRAEs leading to death.
The safety profile of JZP458 is consistent with the published literature on asparaginase given as a component of a multiagent chemotherapeutic regimen.1,2,3,4,5
Rylaze, also known as JZP458, is approved in the
Important Safety Information
RYLAZE should not be given to people who have had:
- Serious allergic reactions to RYLAZE
- Serious swelling of the pancreas (stomach pain), serious blood clots, or serious bleeding during previous asparaginase treatment
RYLAZE may cause serious side effects, including:
- Allergic reactions (a feeling of tightness in your throat, unusual swelling/redness in your throat and/or tongue, or trouble breathing), some of which may be life-threatening
- Swelling of the pancreas (stomach pain)
- Blood clots (may have a headache or pain in leg, arm, or chest)
- Liver problems
Contact your doctor immediately if any of these side effects occur.
Some of the most common side effects with RYLAZE include: liver problems, nausea, bone and muscle pain, tiredness, infection, headache, fever, allergic reactions, fever with low white blood cell count, decreased appetite, mouth swelling (sometimes with sores), bleeding, and too much sugar in the blood.
RYLAZE can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Females of reproductive potential should use effective contraception (other than oral contraceptives) during treatment and for 3 months following the final dose. Do not breastfeed while receiving RYLAZE and for 1 week after the final dose.
Tell your healthcare provider if there are any side effects that are bothersome or that do not go away.
These are not all the possible side effects of RYLAZE. For more information, ask your healthcare provider.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088 (1-800-332-1088).
ALL is a cancer of the blood and bone marrow that can progress quickly if not treated.6 Leukemia is the most common cancer in children, and about three out of four of these cases are ALL.7 Although it is one of the most common cancers in children, ALL is among the most curable of the pediatric malignancies due to recent advancements in treatment.8,9 Adults can also develop ALL, and about four of every 10 cases of ALL diagnosed are in adults.10 The
LBL is a rare, fast-growing, aggressive subtype of Non-Hodgkin's lymphoma, most often seen in teenagers and young adults.6 LBL is a very aggressive lymphoma – also called high-grade lymphoma – which means the lymphoma grows quickly with early spread to different parts of the body.12,13
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1 Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma. 2016;57(4):748–757.
2 Raetz EA, et al. Tolerability and efficacy of L-asparaginase therapy in pediatric patients with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2010;32(7):554-563
3 Vrooman LM, et al. Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia. Pediatr Blood Cancer. 2016;63(2):228-233.
4 Avramis VI, et al. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a
5 van der Sluis IM, et al. Efficacy and safety of recombinant E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the
9 Pui C, Evans W. A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia. Seminars in Hematology. 2013;50(3), 185-196.
11 Salzer W, Bostrom B, Messinger Y et al. 2018. Asparaginase activity levels and monitoring in patients with acute lymphoblastic leukemia. Leukemia & Lymphoma. 59:8, 1797-1806, DOI: 10.1080/10428194.2017.1386305.
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