{"id":"calaspargase","rwe":[],"_fda":{"id":"22da60ef-4135-4bd5-8af1-6d10b7879a0b","set_id":"6585bd0d-bd78-4341-9e87-0f7664821f05","openfda":{"nui":["M0001815","N0000175669"],"unii":["T9FVH03HMZ"],"route":["INTRAVENOUS"],"rxcui":["2121421","2121426"],"spl_id":["22da60ef-4135-4bd5-8af1-6d10b7879a0b"],"brand_name":["asparlas"],"spl_set_id":["6585bd0d-bd78-4341-9e87-0f7664821f05"],"package_ndc":["72694-515-01"],"product_ndc":["72694-515"],"generic_name":["CALASPARGASE PEGOL"],"product_type":["HUMAN PRESCRIPTION DRUG"],"pharm_class_cs":["Asparaginase [CS]"],"substance_name":["CALASPARGASE PEGOL"],"pharm_class_epc":["Asparagine-specific Enzyme [EPC]"],"manufacturer_name":["Servier Pharmaceuticals LLC"],"application_number":["BLA761102"],"is_original_packager":[true]},"version":"12","pregnancy":["8.1 Pregnancy Risk Summary Based on published literature studies with L-asparaginase in pregnant animals, ASPARLAS can cause fetal harm when administered to a pregnant woman. There are no available data on ASPARLAS use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, intravenous administration of calaspargase pegol-mknl to pregnant rats during organogenesis at doses 0.2 to 1 times the maximum recommended human doses did not result in adverse developmental outcomes. Published literature studies in pregnant rabbits, however, suggest asparagine depletion may cause harm to the animal offspring (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal development study, calaspargase pegol-mknl was administered intravenously at doses of 75, 150, and 300 U/kg (0.2, 0.6 and 1 times the maximum recommended human dose, respectively, based on AUC) to pregnant rats during the period of organogenesis. Maternal toxicity of decreased body weight and food consumption was seen at all dose levels resulting in reductions in gravid uterine and placental weights, and slight reductions in fetal body weights. No evidence of structural abnormalities or embryo-fetal mortality were observed in this study at any of the doses tested. Published literature studies in which pregnant rabbits were administered L-asparaginase suggested harm to the animal offspring."],"description":["11 DESCRIPTION Calaspargase pegol-mknl contains an asparagine specific enzyme derived from Escherichia coli , as a conjugate of L-asparaginase (L-asparagine amidohydrolase) and monomethoxypolyethylene glycol (mPEG) with a succinimidyl carbonate (SC) linker. The SC linker is a chemically stable carbamate bond between the mPEG moiety and the lysine groups of L-asparaginase. L-asparaginase is a tetrameric enzyme that is produced endogenously by E. coli and consists of identical 34.5 kDa subunits. Approximately 31 to 39 molecules of SC-PEG are linked to L-asparaginase; the molecular weight of each SC-PEG molecule is about 5 kDa. The activity of ASPARLAS is expressed in units (U). ASPARLAS injection is supplied as a clear, colorless, preservative-free, isotonic sterile solution in phosphate-buffered saline, pH 7.3 that requires dilution prior to intravenous infusion. Each vial of ASPARLAS contains 3,750 units in 5 mL of solution. Each milliliter contains 750 units of calaspargase pegol-mknl; dibasic sodium phosphate, USP (5.58 mg); monobasic sodium phosphate, USP (1.20 mg); and sodium chloride, USP (8.50 mg) in water for injection, USP."],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING ASPARLAS (calaspargase pegol-mknl) injection is supplied as a clear, colorless, preservative-free sterile solution in a single-dose vial containing 3,750 units of calaspargase pegol-mknl per 5 mL solution (NDC 72694-515-01). Store ASPARLAS refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not shake or freeze product. Unopened vials may be stored at room temperature (15°C to 25°C [59°F to 77°F]) for no more than 48 hours."],"pediatric_use":["8.4 Pediatric Use The safety and effectiveness of ASPARLAS in the treatment of ALL have been established in pediatric patients 1 month to <17 years (no data for the age group <1 month old). Use of ASPARLAS in these age groups is supported by evidence from an adequate and well-controlled trial with additional safety from a second trial. The trials included 208 children with ALL or lymphoblastic lymphoma treated with ASPARLAS; there were 19 infants (1 month to <2 years old), 128 children (2 years to <12 years old), and 61 adolescents (12 years to <17 years old). There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups [see Adverse Reactions (6.1) , Clinical Studies (14) ] ."],"effective_time":"20241008","clinical_studies":["14 CLINICAL STUDIES 14.1 Acute Lymphoblastic Leukemia The determination of efficacy was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL using ASPARLAS 2500 U/m 2 intravenously every 3 weeks. The pharmacokinetics of ASPARLAS were studied when used in combination with multiagent chemotherapy in 124 patients with B-cell lineage acute lymphoblastic leukemia (ALL). Among these patients, the median age was 11.5 years (range, 1-26); 62 (50%) were male, 102 (82%) white, 6 (5%) Asian, 5 (4%) Black or African American, 2 (2%) Native Hawaiian or Pacific Islander and 9 (7%) other or unknown. The results showed that 123 (99%, 95% CI: 96%-100%) of the 124 patients maintained NSAA >0.1 U/mL at weeks 6, 12, 18, 24, and 30."],"pharmacodynamics":["12.2 Pharmacodynamics Calaspargase pegol-mknl pharmacodynamic (PD) response was assessed through measurement of plasma and cerebrospinal fluid (CSF) asparagine concentrations via an LC-MS/MS assay. Asparagine concentrations in plasma (N=41) were maintained below the assay limit of quantification for more than 18 days following a single dose of ASPARLAS 2,500 U/m 2 during the induction phase. Mean CSF asparagine concentrations decreased from a pretreatment concentration of 0.8 µg/mL (N=10) to 0.2 µg/mL on Day 4 (N=37) and remained decreased at 0.2 µg/mL (N=35) 25 days after the administration of a single dose of ASPARLAS 2,500 U/m 2 in the induction phase."],"pharmacokinetics":["12.3 Pharmacokinetics Calaspargase pegol-mknl pharmacokinetics (PK) were assessed through measurement of plasma asparaginase activity via a coupled enzymatic assay. The plasma asparaginase activity pharmacokinetics were characterized in 43 patients (1 to 26 years) with newly diagnosed high risk B-precursor ALL treated with a multidrug backbone therapy. Table 3 summarizes the plasma asparaginase activity pharmacokinetic parameters after a single dose of ASPARLAS 2,500 U/m 2 in the induction phase. Table 3: Plasma Asparaginase Activity Pharmacokinetic Parameters After a Single Dose of ASPARLAS 2,500 U/m 2 in Patients with ALL in Study AALL07P4 Parameter Arithmetic Mean (%CV) N=43 General C max (U/mL) 1.62 (23.0) AUC 0-25day (day∙U/mL) 16.9 (23.2) N=42 evaluable subjects. AUC 0∞ (day∙U/mL) T max generally near end of a 1 hour calaspargase pegol-mknl intravenous (IV) infusion. 25.5 (30.4) Absorption T max (h) 1.17 (1.05, 5.47) Median (10 th , 90 th percentiles). Distribution Vss (L) 2.96 (84.3) Elimination t 1/2 (day) Plasma asparaginase activity pharmacokinetics are nonlinear following ASPARLAS administration. 16.1 (51.9) Clearance (L/day) 0.147 (76.1)"],"adverse_reactions":["6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Pancreatitis [see Warnings and Precautions (5.2) ] Thrombosis [see Warnings and Precautions (5.3) ] Hemorrhage [see Warnings and Precautions (5.4) ] Hepatotoxicity, including VOD [see Warnings and Precautions (5.5) ] The most common (incidence ≥10%) grade ≥3 adverse reactions were elevated transaminase, bilirubin increased, pancreatitis, and abnormal clotting studies. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Servier Pharmaceuticals LLC at 1-800-807-6124 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Study DFCI 11-001 The safety of ASPARLAS was investigated in Study DFCI 11-001, an open-label, randomized, active-controlled multicenter clinical trial that treated 237 children and adolescents with newly diagnosed ALL or lymphoblastic lymphoma, with ASPARLAS 2,500 U/m 2 (n=118) or pegaspargase 2,500 U/m 2 (n=119) as part of a Dana-Farber Cancer Institute (DFCI) ALL Consortium backbone therapy. The median age on enrollment was 5 years (range, 1-20 years). The majority of patients were male (62%) and white (70%). Most patients were considered standard risk (SR, 59%) and had B-cell lineage ALL (87%). The median number of doses during the study was 11 doses for ASPARLAS (administered every three weeks) and 16 doses for pegaspargase (administered every two weeks). The median duration of exposure was 8 months for both ASPARLAS and pegaspargase. There was 1 fatal adverse reaction (multi-organ failure in the setting of chronic pancreatitis associated with a pancreatic pseudocyst). Table 2 summarizes the incidence of selected grades ≥3 adverse reactions that occurred in 2 or more patients receiving ASPARLAS. Because not all grade 1 and 2 adverse reactions were collected prospectively, only grade 3 and 4 adverse events are presented in Table 2. Table 2: Selected Grades ≥3 Adverse Reactions in Patients Receiving ASPARLAS with Multi-Agent Chemotherapy (Study DFCI 11-001) ASPARLAS or pegaspargase were administered as a component of multi-agent chemotherapy regimens. Adverse Reaction Grouped terms: Elevated transaminase : Alanine aminotransferase increased, Aspartate aminotransferase increased, Transaminases increased; Bilirubin increased : Bilirubin conjugated increased, Blood bilirubin increased; Pancreatitis : Amylase increased, Lipase increased, Pancreatic necrosis, Pancreatitis, Pancreatitis relapsing; Abnormal clotting studies : Activated partial thromboplastin time prolonged, Blood fibrinogen decreased; Diarrhea : Colitis, Diarrhea, Enterocolitis, Neutropenic colitis; Hypersensitivity : Anaphylactic reaction, Drug hypersensitivity, Hypersensitivity; Embolic and thrombotic events SMQ : Device related thrombosis, Disseminated intravascular coagulation, Embolism, Intracardiac thrombus, Intracranial venous sinus thrombosis, Pulmonary embolism, Superior sagittal sinus thrombosis, Thrombosis in device, Venous thrombosis, Venous thrombosis limb; Sepsis : Bacterial sepsis, Sepsis; Dyspnea : Hypoxia, Respiratory failure; Hemorrhages SMQ (excludes laboratory terms): Disseminated intravascular coagulation, Epistaxis, Hematoma, Hemorrhage intracranial, Melena, Esophageal ulcer hemorrhage, Small intestinal hemorrhage, Upper gastrointestinal hemorrhage; Fungal infection : Fungal infection, Hepatic infection fungal, Respiratory tract infection fungal, Splenic infection fungal, Systemic candida; Pneumonia : Lung infection, Pneumonia, Pneumonitis; Arrhythmia : Atrioventricular block complete, Sinus tachycardia, Ventricular arrhythmia; Cardiac failure : Ejection fraction decreased, Left ventricular dysfunction. ASPARLAS 2,500 U/m 2 N=118 Pegaspargase 2,500 U/m 2 N=119 Grades ≥3 n (%) Grading is based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grades ≥3 n (%) Elevated transaminase 61 (52) 79 (66) Bilirubin increased 24 (20) 30 (25) Pancreatitis 21 (18) 29 (24) Abnormal clotting studies 17 (14) 25 (21) Diarrhea 10 (9) 6 (5) Hypersensitivity 9 (8) 8 (7) Embolic and thrombotic events 9 (8) 10 (8) Sepsis 6 (5) 7 (6) Dyspnea 5 (4) 1 (1) Hemorrhages 5 (4) 5 (4) Fungal infection 4 (3) 3 (3) Pneumonia 4 (3) 8 (7) Arrhythmia 2 (2) 1 (1) Cardiac failure 2 (2) 1 (1) In the subgroup of patients with B-cell lineage ALL, the complete remission rate in the ASPARLAS arm was 98% (95/97), compared to 99% in the pegaspargase arm; the Kaplan-Meier estimates of overall survival of the treatment arms were comparable. Study AALL07P4 The safety of ASPARLAS was also evaluated in Study AALL07P4, an open-label, randomized, active-controlled, multicenter clinical trial that treated patients with newly diagnosed high-risk B-precursor ALL using ASPARLAS 2,500 U/m 2 (n=43) or 2,100 U/m 2 (n=68), or pegaspargase 2,500 U/m 2 (n=52), as a component of an augmented Berlin-Frankfurt-Münster (BFM) therapy regimen. The median age was 11 years (range, 1-26 years); the median duration of exposure was 7 months for both ASPARLAS and pegaspargase. In this study, the induction mortality of patients treated with ASPARLAS was 2.8% (3 out of 111); there were no induction deaths among 52 patients treated with pegaspargase. Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions In Study DFCI 11-001, hypersensitivity reactions occurred in 80% of ASPARLAS-treated patients with new or an increased titer of anti-drug antibodies (ADA) and in 6% of those without ADA [see Clinical Pharmacology (12.6) ] . Two patients with ADA experienced anaphylaxis [see Warnings and Precautions (5.1) ] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of ASPARLAS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hepatic: Veno-occlusive disease"],"contraindications":["4 CONTRAINDICATIONS ASPARLAS is contraindicated in patients with: History of serious hypersensitivity reactions, including anaphylaxis, to pegylated L-asparaginase therapy [see Warnings and Precautions (5.1) ] History of serious pancreatitis during previous L-asparaginase therapy [see Warnings and Precautions (5.2) ] History of serious thrombosis during previous L-asparaginase therapy [see Warnings and Precautions (5.3) ] History of serious hemorrhagic events during previous L-asparaginase therapy [see Warnings and Precautions (5.4) ] Severe hepatic impairment [see Warnings and Precautions (5.5) ] History of serious hypersensitivity reactions to pegylated L-asparaginase. ( 4 ) History of serious thrombosis during L-asparaginase therapy. ( 4 ) History of serious pancreatitis related to previous L-asparaginase treatment. ( 4 ) History of serious hemorrhagic events during previous L-asparaginase therapy. ( 4 ) Severe hepatic impairment. ( 4 )"],"mechanism_of_action":["12.1 Mechanism of Action L-asparaginase is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect of ASPARLAS is thought to be based on the killing of leukemic cells due to depletion of plasma asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival."],"recent_major_changes":["Warnings and Precautions: Hepatotoxicity ( 5.5 ) 11/2023"],"storage_and_handling":["Store ASPARLAS refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not shake or freeze product. Unopened vials may be stored at room temperature (15°C to 25°C [59°F to 77°F]) for no more than 48 hours."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action L-asparaginase is an enzyme that catalyzes the conversion of the amino acid L-asparagine into aspartic acid and ammonia. The pharmacological effect of ASPARLAS is thought to be based on the killing of leukemic cells due to depletion of plasma asparagine. Leukemic cells with low expression of asparagine synthetase have a reduced ability to synthesize asparagine, and therefore depend on an exogenous source of asparagine for survival. 12.2 Pharmacodynamics Calaspargase pegol-mknl pharmacodynamic (PD) response was assessed through measurement of plasma and cerebrospinal fluid (CSF) asparagine concentrations via an LC-MS/MS assay. Asparagine concentrations in plasma (N=41) were maintained below the assay limit of quantification for more than 18 days following a single dose of ASPARLAS 2,500 U/m 2 during the induction phase. Mean CSF asparagine concentrations decreased from a pretreatment concentration of 0.8 µg/mL (N=10) to 0.2 µg/mL on Day 4 (N=37) and remained decreased at 0.2 µg/mL (N=35) 25 days after the administration of a single dose of ASPARLAS 2,500 U/m 2 in the induction phase. 12.3 Pharmacokinetics Calaspargase pegol-mknl pharmacokinetics (PK) were assessed through measurement of plasma asparaginase activity via a coupled enzymatic assay. The plasma asparaginase activity pharmacokinetics were characterized in 43 patients (1 to 26 years) with newly diagnosed high risk B-precursor ALL treated with a multidrug backbone therapy. Table 3 summarizes the plasma asparaginase activity pharmacokinetic parameters after a single dose of ASPARLAS 2,500 U/m 2 in the induction phase. Table 3: Plasma Asparaginase Activity Pharmacokinetic Parameters After a Single Dose of ASPARLAS 2,500 U/m 2 in Patients with ALL in Study AALL07P4 Parameter Arithmetic Mean (%CV) N=43 General C max (U/mL) 1.62 (23.0) AUC 0-25day (day∙U/mL) 16.9 (23.2) N=42 evaluable subjects. AUC 0∞ (day∙U/mL) T max generally near end of a 1 hour calaspargase pegol-mknl intravenous (IV) infusion. 25.5 (30.4) Absorption T max (h) 1.17 (1.05, 5.47) Median (10 th , 90 th percentiles). Distribution Vss (L) 2.96 (84.3) Elimination t 1/2 (day) Plasma asparaginase activity pharmacokinetics are nonlinear following ASPARLAS administration. 16.1 (51.9) Clearance (L/day) 0.147 (76.1) 12.6 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ASPARLAS in the studies described below with the incidence of antibodies in other studies or to other asparaginase products may be misleading. Immunogenicity was assessed using enzyme linked immunosorbent assays (ELISA) in Study DFCI 11-001. Of 98 evaluable patients treated with ASPARLAS, 15 (15%) patients developed new or an increased titer of anti-drug antibodies (ADA) during treatment; 14 of these 15 patients were positive for anti-PEG antibodies. The presence of ADA correlated with the occurrence of hypersensitivity reactions [see Adverse Reactions (6.1) ] . There is insufficient information to determine whether the development of antibodies is associated with altered pharmacokinetics (i.e., loss of asparaginase activity). Specific Populations The impact of renal and hepatic impairment on the PK of calaspargase pegol-mknl is unknown."],"indications_and_usage":["1 INDICATIONS AND USAGE ASPARLAS is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years. ( 1.1 ) 1.1 Acute Lymphoblastic Leukemia ASPARLAS is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS Hypersensitivity : Observe patients for one hour after administration. Discontinue ASPARLAS in patients with serious hypersensitivity reactions. ( 5.1 ) Pancreatitis : Discontinue ASPARLAS in patients with pancreatitis. Monitor blood glucose. ( 5.2 ) Thrombosis : Discontinue ASPARLAS for severe or life-threatening thrombosis. ( 5.3 ) Hemorrhage : Discontinue ASPARLAS for severe or life-threatening hemorrhage. Evaluate for etiology and treat. ( 5.4 ) Hepatotoxicity, including hepatic veno-occlusive disease (VOD) : Monitor for toxicity through recovery from cycle. Discontinue ASPARLAS for severe liver toxicity. ( 5.5 ) 5.1 Hypersensitivity Grade 3 and 4 hypersensitivity reactions, including anaphylaxis, have been reported in clinical trials with ASPARLAS with an incidence between 7 and 21% [see Contraindications (4) , Adverse Reactions (6.1) ] . Hypersensitivity reactions observed with other asparaginases include angioedema, lip swelling, eye swelling, erythema, blood pressure decreased, bronchospasm, dyspnea, pruritus, and rash [see Adverse Reactions (6.1) ] . Premedicate patients 30-60 minutes prior to administration of ASPARLAS [see Dosage and Administration (2.2) ] . Because of the risk of serious allergic reactions (e.g., life-threatening anaphylaxis), administer ASPARLAS in a clinical setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g., epinephrine, oxygen, intravenous steroids, antihistamines) [see Dosage and Administration (2.4) ] and observe patients for 1 hour after administration. Discontinue ASPARLAS in patients with serious hypersensitivity reactions. 5.2 Pancreatitis Cases of pancreatitis have been reported in clinical trials with ASPARLAS with an incidence between 12 and 16% [see Adverse Reactions (6.1) ] . Hemorrhagic or necrotizing pancreatitis have been reported with other asparaginases. Inform patients of the signs and symptoms of pancreatitis, which, if left untreated, could be fatal. Assess serum amylase and/or lipase levels to identify early signs of pancreatic inflammation. Discontinue ASPARLAS if pancreatitis is suspected; if pancreatitis is confirmed, do not resume ASPARLAS [see Dosage and Administration (2.3) ] . 5.3 Thrombosis Serious thrombotic events, including sagittal sinus thrombosis, have been reported in clinical trials with ASPARLAS with an incidence of 9 to 12%. Discontinue ASPARLAS in patients experiencing serious thrombotic events [see Dosage and Administration (2.3) , Adverse Reactions (6.1) ] . 5.4 Hemorrhage Hemorrhage associated with increased prothrombin time (PT), increased partial thromboplastin time (PTT), and hypofibrinogenemia have been reported in patients receiving ASPARLAS [see Adverse Reactions (6.1) ] . Evaluate patients with signs and symptoms of hemorrhage with coagulation parameters including PT, PTT, fibrinogen. Consider appropriate replacement therapy in patients with severe or symptomatic coagulopathy [see Dosage and Administration (2.3) ] . 5.5 Hepatotoxicity, Including Hepatic Veno-Occlusive Disease Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of hepatic veno-occlusive disease (VOD), have been observed in patients treated with ASPARLAS in combination with standard chemotherapy, including during the induction phase of multiphase chemotherapy [see Adverse Reactions (6) ] . Do not administer ASPARLAS to patients with severe hepatic impairment [see Contraindications (4) ] . Evaluate bilirubin and transaminases prior to each dose of ASPARLAS and at least weekly, during cycles of treatment that include ASPARLAS, through 6 weeks after the last dose of ASPARLAS. Monitor frequently for signs and symptoms of hepatic VOD, which may include rapid weight gain, fluid retention with ascites, hepatomegaly (which may be painful), and rapid increase of bilirubin. For patients who develop abnormal liver tests after ASPARLAS, more frequent monitoring for liver test abnormalities and clinical signs and symptoms of VOD is recommended. In the event of serious liver toxicity, including VOD, discontinue treatment with ASPARLAS and provide supportive care [see Dosage and Administration (2.3) ] ."],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility studies have not been conducted with calaspargase pegol-mknl."],"pharmacokinetics_table":["
Table 3: Plasma Asparaginase Activity Pharmacokinetic Parameters After a Single Dose of ASPARLAS 2,500 U/m2 in Patients with ALL in Study AALL07P4
ParameterArithmetic Mean (%CV) N=43
General
Cmax (U/mL)1.62 (23.0)
AUC0-25day (day∙U/mL)16.9 (23.2)N=42 evaluable subjects.
AUC0∞ (day∙U/mL)Tmax generally near end of a 1 hour calaspargase pegol-mknl intravenous (IV) infusion.25.5 (30.4)
Absorption
Tmax (h)1.17 (1.05, 5.47)Median (10th, 90th percentiles).
Distribution
Vss (L)2.96 (84.3)
Elimination
t1/2 (day) Plasma asparaginase activity pharmacokinetics are nonlinear following ASPARLAS administration.16.1 (51.9)
Clearance (L/day)0.147 (76.1)
"],"adverse_reactions_table":["
Table 2: Selected Grades ≥3 Adverse Reactions in Patients Receiving ASPARLAS with Multi-Agent Chemotherapy (Study DFCI 11-001)ASPARLAS or pegaspargase were administered as a component of multi-agent chemotherapy regimens.
Adverse ReactionGrouped terms: Elevated transaminase: Alanine aminotransferase increased, Aspartate aminotransferase increased, Transaminases increased; Bilirubin increased: Bilirubin conjugated increased, Blood bilirubin increased; Pancreatitis: Amylase increased, Lipase increased, Pancreatic necrosis, Pancreatitis, Pancreatitis relapsing; Abnormal clotting studies: Activated partial thromboplastin time prolonged, Blood fibrinogen decreased; Diarrhea: Colitis, Diarrhea, Enterocolitis, Neutropenic colitis; Hypersensitivity: Anaphylactic reaction, Drug hypersensitivity, Hypersensitivity; Embolic and thrombotic events SMQ: Device related thrombosis, Disseminated intravascular coagulation, Embolism, Intracardiac thrombus, Intracranial venous sinus thrombosis, Pulmonary embolism, Superior sagittal sinus thrombosis, Thrombosis in device, Venous thrombosis, Venous thrombosis limb; Sepsis: Bacterial sepsis, Sepsis; Dyspnea: Hypoxia, Respiratory failure; Hemorrhages SMQ (excludes laboratory terms): Disseminated intravascular coagulation, Epistaxis, Hematoma, Hemorrhage intracranial, Melena, Esophageal ulcer hemorrhage, Small intestinal hemorrhage, Upper gastrointestinal hemorrhage; Fungal infection: Fungal infection, Hepatic infection fungal, Respiratory tract infection fungal, Splenic infection fungal, Systemic candida; Pneumonia: Lung infection, Pneumonia, Pneumonitis; Arrhythmia: Atrioventricular block complete, Sinus tachycardia, Ventricular arrhythmia; Cardiac failure: Ejection fraction decreased, Left ventricular dysfunction.ASPARLAS 2,500 U/m2 N=118Pegaspargase 2,500 U/m2 N=119
Grades ≥3 n (%)Grading is based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.Grades ≥3 n (%)
Elevated transaminase61 (52)79 (66)
Bilirubin increased24 (20)30 (25)
Pancreatitis21 (18)29 (24)
Abnormal clotting studies17 (14)25 (21)
Diarrhea10 (9)6 (5)
Hypersensitivity9 (8)8 (7)
Embolic and thrombotic events9 (8)10 (8)
Sepsis6 (5)7 (6)
Dyspnea5 (4)1 (1)
Hemorrhages5 (4)5 (4)
Fungal infection4 (3)3 (3)
Pneumonia4 (3)8 (7)
Arrhythmia2 (2)1 (1)
Cardiac failure2 (2)1 (1)
"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Hypersensitivity Inform patients on the possibility of serious allergic reactions, including anaphylaxis. Instruct the patient on the symptoms of allergic reactions and to seek medical advice immediately if they experience such symptoms [see Warnings and Precautions (5.1) ] . Pancreatitis Instruct patients on the signs and symptoms of pancreatitis and to seek immediate medical attention if they experience severe abdominal pain [see Warnings and Precautions (5.2) ] . Instruct patients on the risk of hyperglycemia and glucose intolerance. Advise patients to seek medical advice if they experience excessive thirst or any increase in the volume or frequency of urination [see Dosage and Administration (2.3) ] . Thrombosis Instruct patients on the risk of thrombosis and to seek medical advice immediately if they experience severe headache, arm or leg swelling, shortness of breath, or chest pain [see Warnings and Precautions (5.3) ] . Hemorrhage Advise patients to report any unusual bleeding or bruising to their healthcare provider [see Warnings and Precautions (5.4) ] . Hepatotoxicity , including Veno-Occlusive Liver Disease (VOD) Inform patients that liver problems, including severe, life-threatening, or fatal VOD and abnormalities in liver tests, may develop during ASPARLAS treatment. Advise patients to contact their healthcare provider immediately if they experience jaundice, rapid weight gain, abdominal swelling, or right upper abdominal pain or tenderness [see Warnings and Precautions (5.5) ] . Pregnancy Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ASPARLAS and for 3 months after the last dose [see Use in Specific Populations (8.3) ]. Lactation Advise women not to breastfeed during treatment with ASPARLAS and for at least 3 months after the last dose [see Use in Specific Populations (8.2) ] ."],"spl_unclassified_section":["Manufactured by: Servier Pharmaceuticals LLC Boston, MA 02210 U.S. License No. 2125 ASPARLAS is a registered trademark of Servier IP UK Ltd, a wholly owned, indirect subsidiary of Les Laboratoires Servier. Servier and the Servier logo are trademarks of Les Laboratoires Servier. I-008-21-US-E ASP-005"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION Recommended Dosage: 2,500 units/m 2 intravenously no more frequently than every 21 days. ( 2.1 ) See Full Prescribing Information for important details regarding dosing modifications and preparation and administration. ( 2.2 , 2.3 , 2.4 ) 2.1 Recommended Dosage The recommended dose of ASPARLAS is 2,500 units/m 2 given intravenously no more frequently than every 21 days. 2.2 Recommended Premedication Premedicate patients with acetaminophen, an H-1 receptor blocker (such as diphenhydramine), and an H-2 receptor blocker (such as famotidine) 30-60 minutes prior to administration of ASPARLAS to decrease the risk and severity of both infusion and hypersensitivity reactions [see Warnings and Precautions (5.1) ] . 2.3 Recommended Monitoring and Dosage Modifications for Adverse Reactions Monitor patients at least weekly with bilirubin, transaminases, glucose, and clinical examinations until recovery from the cycle of therapy. If an adverse reaction should occur, modify treatment according to Table 1. Table 1: Dosage Modifications Adverse Reaction Severity Grade 1 is mild, grade 2 is moderate, grade 3 is severe, and grade 4 is life-threatening. Action Infusion Reaction/ Hypersensitivity Reaction [see Warnings and Precautions (5.1) ] Grade 1 Reduce the infusion rate by 50% Grade 2 Interrupt the infusion of ASPARLAS Treat the symptoms When symptoms resolve, resume the infusion and reduce the infusion rate by 50% Grade 3 to 4 Discontinue ASPARLAS permanently Pancreatitis [see Warnings and Precautions (5.2) ] Grades 3 to 4 Hold ASPARLAS for elevations in lipase or amylase >3 × upper limit of normal (ULN) until enzyme levels stabilize or are declining Discontinue ASPARLAS permanently if clinical pancreatitis is confirmed Thrombosis [see Warnings and Precautions (5.3) ] Uncomplicated deep vein thrombosis Hold ASPARLAS Treat with appropriate antithrombotic therapy Upon resolution of symptoms consider resuming ASPARLAS, while continuing antithrombotic therapy Severe or life-threatening thrombosis Discontinue ASPARLAS permanently Treat with appropriate antithrombotic therapy Hemorrhage [see Warnings and Precautions (5.4) ] Grade 3 to 4 Hold ASPARLAS Evaluate for coagulopathy and consider clotting factor replacement as needed Resume ASPARLAS with the next scheduled dose if bleeding is controlled Hepatotoxicity [see Warnings and Precautions (5.5) ] Total bilirubin more than 3 times to no more than 10 times the ULN Hold ASPARLAS until total bilirubin is ≤1.5 times the ULN Total bilirubin more than 10 times the ULN Discontinue ASPARLAS and do not make up for missed doses 2.4 Preparation and Administration ASPARLAS is a clear and colorless solution. Visually inspect parenteral drug products for particulate matter, cloudiness, or discoloration prior to administration. If any of these are present, discard the vial. Do not administer if ASPARLAS has been shaken or vigorously agitated, frozen, or stored at room temperature for more than 48 hours. Dilute ASPARLAS in 100 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP using sterile/aseptic technique. Discard any unused portion left in a vial. After dilution, administer immediately into a running infusion of either 0.9% sodium chloride or 5% dextrose, respectively. Administer the dose over a period of 1 hour. Do not infuse other drugs through the same intravenous line during administration of ASPARLAS. The diluted solution may be stored for up to 4 hours at room temperature (15°C to 25°C [59°F to 77°F]) or refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours. Protect from light. Do not shake or freeze."],"spl_product_data_elements":["asparlas calaspargase pegol CALASPARGASE PEGOL CALASPARGASE PEGOL SODIUM PHOSPHATE, MONOBASIC, DIHYDRATE SODIUM PHOSPHATE, DIBASIC, UNSPECIFIED FORM SODIUM CHLORIDE WATER"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS Injection: 3,750 units/5 mL (750 units/mL) clear, colorless solution in a single-dose vial. Injection: 3,750 units/5 mL (750 units/mL) in a single-dose vial. ( 3 )"],"recent_major_changes_table":["
Warnings and Precautions: Hepatotoxicity (5.5)11/2023
"],"clinical_pharmacology_table":["
Table 3: Plasma Asparaginase Activity Pharmacokinetic Parameters After a Single Dose of ASPARLAS 2,500 U/m2 in Patients with ALL in Study AALL07P4
ParameterArithmetic Mean (%CV) N=43
General
Cmax (U/mL)1.62 (23.0)
AUC0-25day (day∙U/mL)16.9 (23.2)N=42 evaluable subjects.
AUC0∞ (day∙U/mL)Tmax generally near end of a 1 hour calaspargase pegol-mknl intravenous (IV) infusion.25.5 (30.4)
Absorption
Tmax (h)1.17 (1.05, 5.47)Median (10th, 90th percentiles).
Distribution
Vss (L)2.96 (84.3)
Elimination
t1/2 (day) Plasma asparaginase activity pharmacokinetics are nonlinear following ASPARLAS administration.16.1 (51.9)
Clearance (L/day)0.147 (76.1)
"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on published literature studies with L-asparaginase in pregnant animals, ASPARLAS can cause fetal harm when administered to a pregnant woman. There are no available data on ASPARLAS use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, intravenous administration of calaspargase pegol-mknl to pregnant rats during organogenesis at doses 0.2 to 1 times the maximum recommended human doses did not result in adverse developmental outcomes. Published literature studies in pregnant rabbits, however, suggest asparagine depletion may cause harm to the animal offspring (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal Data In an embryo-fetal development study, calaspargase pegol-mknl was administered intravenously at doses of 75, 150, and 300 U/kg (0.2, 0.6 and 1 times the maximum recommended human dose, respectively, based on AUC) to pregnant rats during the period of organogenesis. Maternal toxicity of decreased body weight and food consumption was seen at all dose levels resulting in reductions in gravid uterine and placental weights, and slight reductions in fetal body weights. No evidence of structural abnormalities or embryo-fetal mortality were observed in this study at any of the doses tested. Published literature studies in which pregnant rabbits were administered L-asparaginase suggested harm to the animal offspring. 8.2 Lactation Risk Summary There are no data on the presence of calaspargase pegol-mknl in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with ASPARLAS and for 3 months after the last dose. 8.3 Females and Males of Reproductive Potential ASPARLAS can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Pregnancy testing is recommended in females of reproductive potential prior to initiating ASPARLAS. Contraception Advise females of reproductive potential to use effective non-hormonal contraceptive methods during treatment with ASPARLAS and for at least 3 months after the last dose. 8.4 Pediatric Use The safety and effectiveness of ASPARLAS in the treatment of ALL have been established in pediatric patients 1 month to <17 years (no data for the age group <1 month old). Use of ASPARLAS in these age groups is supported by evidence from an adequate and well-controlled trial with additional safety from a second trial. The trials included 208 children with ALL or lymphoblastic lymphoma treated with ASPARLAS; there were 19 infants (1 month to <2 years old), 128 children (2 years to <12 years old), and 61 adolescents (12 years to <17 years old). There were no clinically meaningful differences in safety or nadir serum asparaginase activity across age groups [see Adverse Reactions (6.1) , Clinical Studies (14) ] ."],"dosage_and_administration_table":["
Table 1: Dosage Modifications
Adverse ReactionSeverityGrade 1 is mild, grade 2 is moderate, grade 3 is severe, and grade 4 is life-threatening.Action
Infusion Reaction/ Hypersensitivity Reaction [see Warnings and Precautions (5.1)]Grade 1Reduce the infusion rate by 50%
Grade 2Interrupt the infusion of ASPARLASTreat the symptomsWhen symptoms resolve, resume the infusion and reduce the infusion rate by 50%
Grade 3 to 4Discontinue ASPARLAS permanently
Pancreatitis [see Warnings and Precautions (5.2)]Grades 3 to 4 Hold ASPARLAS for elevations in lipase or amylase >3 × upper limit of normal (ULN) until enzyme levels stabilize or are decliningDiscontinue ASPARLAS permanently if clinical pancreatitis is confirmed
Thrombosis [see Warnings and Precautions (5.3)]Uncomplicated deep vein thrombosisHold ASPARLASTreat with appropriate antithrombotic therapyUpon resolution of symptoms consider resuming ASPARLAS, while continuing antithrombotic therapy
Severe or life-threatening thrombosisDiscontinue ASPARLAS permanentlyTreat with appropriate antithrombotic therapy
Hemorrhage [see Warnings and Precautions (5.4)]Grade 3 to 4Hold ASPARLASEvaluate for coagulopathy and consider clotting factor replacement as neededResume ASPARLAS with the next scheduled dose if bleeding is controlled
Hepatotoxicity [see Warnings and Precautions (5.5)]Total bilirubin more than 3 times to no more than 10 times the ULNHold ASPARLAS until total bilirubin is ≤1.5 times the ULN
Total bilirubin more than 10 times the ULNDiscontinue ASPARLAS and do not make up for missed doses
"],"package_label_principal_display_panel":["PRINCIPAL DISPLAY PANEL - 5 mL Vial Carton NDC 72694-515-01 ASPARLAS ® calaspargase pegol-mknl Injection 3750 units/5 mL (750 units/mL) For Intravenous Infusion Only One single-dose vial. Discard unused portion. Must dilute before use. Rx ONLY SERVIER PRINCIPAL DISPLAY PANEL - 5 mL Vial Carton"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity, mutagenicity, and impairment of fertility studies have not been conducted with calaspargase pegol-mknl."]},"tags":[],"safety":{"boxedWarnings":[],"safetySignals":[{"date":"","signal":"HYPERSENSITIVITY","source":"FDA FAERS","actionTaken":"183 reports"},{"date":"","signal":"ANAPHYLACTIC REACTION","source":"FDA FAERS","actionTaken":"89 reports"},{"date":"","signal":"PANCREATITIS","source":"FDA FAERS","actionTaken":"62 reports"},{"date":"","signal":"INFUSION RELATED REACTION","source":"FDA FAERS","actionTaken":"52 reports"},{"date":"","signal":"HYPERTRIGLYCERIDAEMIA","source":"FDA FAERS","actionTaken":"44 reports"},{"date":"","signal":"VOMITING","source":"FDA FAERS","actionTaken":"33 reports"},{"date":"","signal":"FEBRILE NEUTROPENIA","source":"FDA FAERS","actionTaken":"29 reports"},{"date":"","signal":"NEUTROPENIA","source":"FDA FAERS","actionTaken":"25 reports"},{"date":"","signal":"TACHYCARDIA","source":"FDA FAERS","actionTaken":"22 reports"},{"date":"","signal":"NAUSEA","source":"FDA FAERS","actionTaken":"21 reports"}],"drugInteractions":[{"drug":"Warfarin","action":"Monitor","effect":"Increased risk of bleeding"},{"drug":"Heparin","action":"Monitor","effect":"Increased risk of bleeding"},{"drug":"Other anticoagulants","action":"Monitor","effect":"Increased risk of bleeding"},{"drug":"Aspirin","action":"Monitor","effect":"Increased risk of bleeding"},{"drug":"Nonsteroidal anti-inflammatory drugs (NSAIDs)","action":"Monitor","effect":"Increased risk of bleeding"},{"drug":"Thrombolytics","action":"Avoid","effect":"Increased risk of bleeding"},{"drug":"Other antineoplastic agents","action":"Monitor","effect":"Increased risk of bleeding"},{"drug":"Live vaccines","action":"Avoid","effect":"Risk of vaccine failure"},{"drug":"Other vaccines","action":"Avoid","effect":"Risk of vaccine failure"}],"commonSideEffects":[{"effect":"Elevated transaminase","drugRate":"≥10%","severity":"Grade ≥3","_validated":true},{"effect":"Bilirubin increased","drugRate":"≥10%","severity":"Grade ≥3","_validated":true},{"effect":"Pancreatitis","drugRate":"≥10%","severity":"Grade ≥3","_validated":true},{"effect":"Abnormal clotting studies","drugRate":"≥10%","severity":"Grade ≥3","_validated":true}],"contraindications":["History of serious hypersensitivity reactions, including anaphylaxis, to pegylated L-asparaginase therapy","History of serious pancreatitis during previous L-asparaginase therapy","History of serious thrombosis during previous L-asparaginase therapy","History of serious hemorrhagic events during previous L-asparaginase therapy","Severe hepatic impairment"],"specialPopulations":{"Lactation":"There are no data on the presence of calaspargase pegol-mknl in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with ASPARLAS and for 3 months after the last dose.","Pregnancy":"Based on published literature studies with L-asparaginase in pregnant animals, ASPARLAS can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively.","Geriatric use":"Not mentioned","Pediatric use":"The safety and effectiveness of ASPARLAS in the treatment of ALL have been established in pediatric patients 1 month to <17 years (no data for the age group <1 month old). Use of ASPARLAS in these age groups is supported by evidence from an adequate and well-controlled trial with additional safety from a second trial.","Females and Males of Reproductive Potential":"ASPARLAS can cause fetal harm when administered to a pregnant woman. Pregnancy testing is recommended in females of reproductive potential prior to initiating ASPARLAS. Contraception Advise females of reproductive potential to use effective non-hormonal contraceptive methods during treatment with ASPARLAS and for at least 3 months after the last dose."}},"trials":[],"_chembl":{"chemblId":"CHEMBL2108728","moleculeType":"Enzyme"},"aliases":[],"company":"Pfizer","patents":[],"pricing":[],"_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=calaspargase","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-19T23:51:43.048646+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Calaspargase","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-19T23:51:51.242632+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-19T23:51:49.807290+00:00"},"regulatory.eu":{"url":"","method":"api_direct","source":"European Medicines Agency","rawText":"","confidence":1,"sourceType":"ema_api","retrievedAt":"2026-04-19T23:51:43.120124+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-19T23:51:42.157941+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=calaspargase","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T23:51:50.119847+00:00"},"mechanism.drugClass":{"url":"https://api.fda.gov/drug/label.json","method":"deterministic","source":"FDA Label (EPC)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:51:41.376664+00:00"},"administration.route":{"url":"","method":"deterministic","source":"FDA Label","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:51:41.376703+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (no boxed warning)","rawText":"","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:51:41.376708+00:00"},"safety.safetySignals":{"url":"https://api.fda.gov/drug/event.json","method":"api_direct","source":"FDA FAERS","rawText":"","confidence":1,"sourceType":"fda_faers","retrievedAt":"2026-04-19T23:51:51.635106+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: Asparagine hydrolytic enzyme","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:51:51.242572+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2108728/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:51:50.894480+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"BLA761102","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:51:41.376711+00:00"}},"allNames":"asparlas","offLabel":[],"timeline":[{"date":"2018-12-01","type":"positive","_source":"Wikipedia","milestone":"Calaspargase pegol-mknl approved in the United States","regulator":"FDA"},{"date":"2018-12-20","type":"positive","_source":"FDA BLA761102","milestone":"FDA ORIG — SERVIER PHARMA LLC","regulator":"FDA","description":""},{"date":"2019-09-05","type":"positive","_source":"FDA BLA761102","milestone":"FDA SUPPL — SERVIER PHARMA LLC","regulator":"FDA","description":""},{"date":"2020-06-24","type":"positive","_source":"FDA BLA761102","milestone":"FDA SUPPL — SERVIER PHARMA LLC","regulator":"FDA","description":""},{"date":"2021-12-21","type":"positive","_source":"FDA BLA761102","milestone":"FDA SUPPL — SERVIER PHARMA LLC","regulator":"FDA","description":""},{"date":"2023-11-29","type":"positive","_source":"FDA BLA761102","milestone":"FDA SUPPL — SERVIER PHARMA LLC","regulator":"FDA","description":""}],"_dailymed":{"setId":"6585bd0d-bd78-4341-9e87-0f7664821f05","title":"ASPARLAS (CALASPARGASE PEGOL) INJECTION, SOLUTION [SERVIER PHARMACEUTICALS LLC]","labeler":""},"aiSummary":"Calaspargase, marketed by Pfizer Inc., is an L-asparaginase enzyme used in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and young adult patients. It works by depleting plasma asparagine, which is critical for the survival of leukemic cells. Common adverse reactions include elevated transaminase, increased bilirubin, pancreatitis, and abnormal clotting studies. The drug is contraindicated in patients with a history of serious hypersensitivity, pancreatitis, thrombosis, hemorrhagic events, or severe hepatic impairment during previous L-asparaginase therapy.","brandName":"Asparlas","ecosystem":[],"isGeneric":true,"mechanism":{"target":"L-asparagine","novelty":"Calaspargase is a pegylated form of L-asparaginase, designed to improve stability and reduce immunogenicity compared to native L-asparaginase.","modality":"Enzyme Therapy","drugClass":"Asparagine-specific Enzyme [EPC]","explanation":"The pharmacological effect of Calaspargase is based on the depletion of plasma asparagine, which is essential for the survival of leukemic cells with low expression of asparagine synthetase.","oneSentence":"Calaspargase is an L-asparaginase enzyme that catalyzes the conversion of L-asparagine into aspartic acid and ammonia, leading to the depletion of plasma asparagine and the death of leukemic cells.","technicalDetail":"L-asparaginase catalyzes the hydrolysis of L-asparagine to aspartic acid and ammonia, thereby depleting plasma asparagine levels. Leukemic cells, which have a reduced ability to synthesize asparagine, become starved and die."},"_companyIR":{"url":"https://www.pfizer.com/investors","revenueRefs":[],"pipelineRefs":[]},"_scrapedAt":"2026-03-28T01:48:00.620Z","_scrapedBy":"cloudflare-swarm","_wikipedia":{"title":"Calaspargase pegol","extract":"Calaspargase pegol, sold under the brand name Asparlas, is a medication for the treatment of acute lymphoblastic leukemia (ALL). It is approved in the United States as a component of a multi-agent chemotherapeutic regimen for ALL in pediatric and young adult patients aged one month to 21 years.","wiki_history":"==History==\nIn December 2018, calaspargase pegol-mknl was approved in the United States as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age one month to 21 years.\n\nApproval was based on a demonstration of the achievement and maintenance of nadir serum asparaginase activity above the level of 0.1 U/mL when using calaspargase pegol-mknl, 2500 U/m2 intravenously, every three weeks. The pharmacokinetics of calaspargase pegol-mknl were studied when administered in combination with multiagent chemotherapy in 124 subjects with B-cell lineage ALL.\n\nThe FDA approved calaspargase pegol-mknl based on evidence primarily from two clinical trials (Trial 1/NCT01574274 and Trial 2/AALL07P4) of 237 subjects with acute lymphoblastic leukemia (ALL). The trials were conducted in the United States and Canada.\n\nTrial 1 enrolled subjects 1 to 20 years old who were recently diagnosed with ALL or lymphoblastic lymphoma. Subjects received calaspargase pegol-mknl or pegaspargase (a drug that helps convert asparagine to other substances) as part of a combination of drugs used for treatment of ALL. The trial had 2 phases. Subjects received calaspargase pegol-mknl or pegaspargase intravenously on Day 7 of the first phase. Subjects received either calaspargase pegol-mknl intravenously every 3 weeks for 10 doses or pegaspargase intravenously every 2 weeks for 15 doses during the second phase. The benefit of calaspargase pe"},"commercial":{"yoyGrowth":"","launchDate":"2018","annualCostUS":"Not available","_launchSource":"FDA BLA761102 (SERVIER PHARMA LLC)","genericStatus":"Generic — off-patent","currentRevenue":"Not available","manufacturerCount":"1 approved manufacturers","patientPopulation":"Pediatric and young adult patients age 1 month to 21 years with acute lymphoblastic leukemia","peakSalesEstimate":"Not available"},"references":[{"id":1,"url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=calaspargase","fields":["mechanism","safety","indications","administration"],"source":"FDA Drug Label (DailyMed)"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=calaspargase","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=calaspargase","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://www.ebi.ac.uk/chembl/","fields":["molecular"],"source":"ChEMBL (EMBL-EBI)"},{"id":5,"url":"https://en.wikipedia.org/wiki/calaspargase","fields":["history","overview"],"source":"Wikipedia"},{"id":6,"url":"https://www.accessdata.fda.gov/scripts/cder/daf/","fields":["timeline","launchDate"],"source":"FDA Drugs@FDA"},{"id":7,"url":"https://open.fda.gov/apis/drug/event/","fields":["safetySignals"],"source":"FDA FAERS"},{"id":8,"url":"https://www.ema.europa.eu/","fields":["regulatoryStatus"],"source":"European Medicines Agency (EMA)"},{"id":9,"url":"https://www.whocc.no/atc_ddd_index/","fields":["classification"],"source":"WHO ATC/DDD Index"},{"id":10,"url":"https://list.essentialmeds.org/","fields":["regulatoryStatus"],"source":"WHO Essential Medicines List"},{"id":11,"url":"https://www.accessdata.fda.gov/scripts/cder/daf/","fields":["genericManufacturers"],"source":"FDA Drugs@FDA (ANDA/BLA)"}],"_tgaChecked":true,"_validation":{"fieldsValidated":0,"lastValidatedAt":"2026-04-19T23:51:54.206774+00:00","fieldsConflicting":0,"overallConfidence":0.95},"_whoChecked":true,"biosimilars":[],"competitors":[{"name":"asparlas","slug":"calaspargase-pegol","company":"Servier Pharmaceuticals LLC","advantage":"Same class (Asparagine-specific Enzyme [EPC])","genericName":"CALASPARGASE PEGOL"},{"name":"Rylaze","slug":"asparaginase-erwinia-chrysanthemi-(recombinant)-rywn","company":"Jazz Pharmaceuticals, Inc.","advantage":"Same class (Asparagine-specific Enzyme [EPC])","genericName":"ASPARAGINASE ERWINIA CHRYSANTHEMI (RECOMBINANT)-RYWN"},{"name":"ONCASPAR","slug":"pegaspargase","company":"Servier Pharmaceuticals LLC","advantage":"Same class (Asparagine-specific Enzyme [EPC])","genericName":"PEGASPARGASE"}],"genericName":"calaspargase","indications":{"approved":[{"name":"Acute Lymphoblastic Leukemia (ALL) in pediatric and adult patients","regulator":"FDA"},{"name":"Acute Lymphoblastic Leukemia (ALL) in pediatric patients","regulator":"FDA"}],"offLabel":[],"pipeline":[]},"_mhraChecked":true,"labelChanges":[],"relatedDrugs":[],"trialDetails":[{"nctId":"NCT06317662","phase":"PHASE2","title":"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","status":"RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2025-06-05","conditions":"Acute Leukemia of Ambiguous Lineage, B Acute Lymphoblastic Leukemia","enrollment":153},{"nctId":"NCT06561074","phase":"PHASE2","title":"A Phase 2 Study to Evaluate Efficacy of Calaspargase Pegol-mknl and Decitabine Combined With Venetoclax in Pediatric, Adolescent, and Young Adult Patients With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL) and T- Cell Lymphoblastic Lymphoma (T-LLy)","status":"RECRUITING","sponsor":"M.D. Anderson Cancer Center","startDate":"2025-09-25","conditions":"T-cell Acute Lymphoblastic Leukemia, T-Cell Lymphoblastic Lymphoma","enrollment":22},{"nctId":"NCT06124157","phase":"PHASE3","title":"A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)","status":"RECRUITING","sponsor":"National Cancer Institute (NCI)","startDate":"2025-05-30","conditions":"B Acute Lymphoblastic Leukemia","enrollment":222},{"nctId":"NCT05602194","phase":"PHASE3","title":"Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma","status":"RECRUITING","sponsor":"Children's Oncology Group","startDate":"2023-08-14","conditions":"B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, B Acute Lymphoblastic Leukemia, BCR-ABL1-Like","enrollment":440},{"nctId":"NCT05292664","phase":"PHASE1","title":"Venetoclax Basket Trial for High Risk Hematologic Malignancies","status":"RECRUITING","sponsor":"Andrew E. 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