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Xenpozyme is a brand name for Olipudase Alfa. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Xenpozyme is indicated as an enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B.
Verbatim from this product's EMA label. Tap a section to expand.
Xenpozyme treatment should be supervised by a healthcare professional experienced in the management of ASMD or other inherited metabolic disorders. Xenpozyme infusion should be 3 administered by a healthcare professional with access to appropriate medical support to manage potential severe reactions such as serious systemic hypersensitivity reactions.
Posology The rapid metabolism of accumulated sphingomyelin (SM) by olipudase alfa generates pro-inflammatory breakdown products, which may induce infusion-associated reactions and/or transient liver enzyme elevations. Treatment with Xenpozyme must always be initiated via a dose escalation regimen (see below) to minimise the risk of infusion-associated reactions, including acute phase reactions, and increases in liver transaminases.
9). Please note that the dose escalation for paediatric patients differs from the one for adults. In addition to the dose escalation regimen, each dose must be administered using a staggered infusion rate (see Tables 3 and 4). For missed doses see also below.
Home infusion for patients should only be considered after the dose escalation phase. Xenpozyme dose is based on the actual body weight for patient with a body mass index (BMI) ≤ 30 or an optimal body weight for patient with a BMI > 30 (see section for patients with a BMI > 30).
1 mg/kg* for adults (also see missed doses subsection for additional guidance) and subsequently, the dose should be increased according to the dose escalation regimen presented in Table 1: Table 1: Dose escalation regimen in adults *Actual body weight will be used for patients with a BMI ≤ 30.
For patients with a BMI > 30, an optimal body weight will be used as described below. Maintenance phase The recommended maintenance dose of Xenpozyme is 3 mg/kg* every 2 weeks. *Actual body weight will be used for patients with a BMI ≤ 30.
For patients with a BMI > 30, an optimal body weight will be used as described below. 6 mg/kg* Seventh dose (Week 12) 1 mg/kg* Eighth dose (Week 14) 2 mg/kg* Ninth dose (Week 16) 3 mg/kg* (recommended maintenance dose) *Actual body weight will be used for patients with a BMI ≤ 30.
For patients with a BMI > 30, an optimal body weight will be used as described below. Maintenance phase The recommended maintenance dose of Xenpozyme is 3 mg/kg* every 2 weeks. *Actual body weight will be used for patients with a BMI ≤ 30.
5%) adult patient, and anaphylactic reaction, urticaria, rash, hypersensitivity, and alanine aminotransferase level increase, each in 1 (5%) paediatric patient. The incidence of serious hypersensitivity-related IARs were higher in paediatric patients compared to adults.
One adult patient discontinued due to recurrent adverse events of rash. 7%). Tabulated list of adverse reactions The pooled safety analysis from 4 clinical studies (a tolerability study in adult patients, ASCEND, ASCEND-Peds, and an extension study in adult and paediatric patients) included a total of 60 patients (40 adult and 20 paediatric patients) treated with Xenpozyme at doses up to 3 mg/kg every 2 weeks.
Adverse reactions reported in the pooled safety analysis of clinical studies are listed in Table 5 per System Organ Class, presented by frequency categories: very common (≥1/10), common (≥1/100 to<1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000) and not known (cannot be estimated from the available data).
5% of adult and 65% of paediatric patients. 5%). IAR symptoms reported most frequently in paediatric patients were pyrexia (40%), urticaria (40%), vomiting (30%), C-reactive protein increased (20%), headache (20%), nausea (20%), erythema (15%), rash (15%), serum ferritin increased (15%), abdominal pain (10%), and pruritus (10%).
IARs typically occurred between the time of infusion and 24 hours after infusion end. 5% adult and 45% paediatric patients in clinical studies. 3%). Anaphylactic reactions were reported in paediatric patients in the clinical studies and in the post- marketing setting.
Anti-olipudase alfa IgE antibodies were detected in some of those patients. 11 Although a tailored desensitisation regimen enabled certain patients to resume long term treatment at the recommended maintenance dose, there are also cases where desensitisation was unsuccessful, and treatment had to be stopped due to anaphylactic reactions before reaching the maintenance dose.
Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered medicinal product should be clearly recorded. Absence of blood-brain barrier transfer Xenpozyme is not expected to cross the blood-brain barrier or modulate the CNS manifestations of the disease.
Infusion associated reactions (IARs) IARs occurred in approximately 60% of patients treated with Xenpozyme in clinical studies. 8). 8). IARs typically occurred between the time of infusion and up to 24 hours after infusion completion.
9). 8). 5%) adult and 9 (45%) paediatric patients including one paediatric patient who experienced anaphylaxis. Management Patients should be observed closely during and for an appropriate period of time after the infusion, based on clinical judgement.
Patients must be informed of the potential symptoms of hypersensitivity/anaphylaxis and instructed to seek immediate medical care should symptoms occur. IARs management should be based on the severity of signs and symptoms and may include temporarily interrupting the Xenpozyme infusion, lowering the infusion rate, and/or appropriate medical treatment.
8 If severe hypersensitivity or anaphylaxis occurs, Xenpozyme should be discontinued immediately, and appropriate medical treatment should be initiated. The prescriber should evaluate the risks and benefits of Xenpozyme re-administration following anaphylaxis or severe hypersensitivity reaction.
If considering re-administration of Xenpozyme following anaphylaxis, the prescribing physician should contact the local Sanofi representative for advice on re-administration. 8). In such patients, extreme caution should be exercised, with appropriate resuscitation measures available, when Xenpozyme is readministered.
If mild or moderate IARs occur, the infusion rate may be slowed or temporarily stopped, the duration of each step for an individual infusion increased, and/or the Xenpozyme dose reduced. 2). Patients may be pre-treated with antihistamines, antipyretics, and/or glucocorticoids to prevent or reduce allergic reactions.
4).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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For patients with a BMI > 30, an optimal body weight will be used as described below. Patients with BMI> 30 In adult and paediatric patients with a body mass index (BMI) > 30, the body weight that is used to calculate the dose of Xenpozyme is estimated via the following method (for dose escalation and maintenance phases).
7 m. 7 kg. Missed doses A dose is considered missed when not administered within 3 days of the scheduled date. When a dose of Xenpozyme is missed, the next dose should be administered as described below as soon as possible. Thereafter, administrations should be scheduled every 2 weeks from the date of the last administration.
9). A patient who has not been largely debulked or has suspected re-accumulation, due to missed doses, should resume treatment at a lower dose.
Table 2B:
Xenpozyme dosing recommendations for adult and paediatric patients after one or several missed dose(s). Consecutive missed doses Dose escalation phase Maintenance phase If 1 infusion is missed*: The last tolerated dose should be administered, before resuming dose escalation according to the regimen in adults (Table 1) or in paediatric patients (Table 2A).
The maintenance dose should be administered and the treatment schedule adjusted accordingly. 6 mg/kg, that dose should be administered twice as per Table 1 and Table 2A. 4). If the pre-infusion transaminase levels are elevated above baseline and >2 times the upper limit of normal (ULN), the Xenpozyme dose can be adjusted (prior dose repeated or reduced) or treatment can be temporarily withheld in accordance with the degree of transaminase elevation.
If a patient requires a dose adjustment or treatment […]
g C-reactive protein, ferritin value) indicative of acute phase reaction. Transaminase elevations Transient transaminase (ALT or AST) elevations within 24 to 48 hours after an infusion occurred in some patients treated with Xenpozyme during the dose escalation phase in the clinical studies.
These elevations generally returned to the previous pre-infusion transaminase levels by the next scheduled infusion. 2%, compared to baseline. In adult patients, all 16 patients with an elevated baseline ALT had an ALT within the normal range and 10 of 12 patients with an elevated baseline AST had an AST within the normal range.
5%) adult patients and 15 out of 20 (75%) paediatric patients treated with Xenpozyme developed treatment-emergent anti-drug antibodies (ADA). The median time to seroconversion from first Xenpozyme infusion was approximately 52 weeks in adults and 12 weeks in paediatric patients.
The majority of ADA-positive patients ( 16 out of 19 adult and 10 out of 15 paediatric patients) had a low ADA response (peak titer ≤ 400) or reverted to ADA-negative. Three adult ADA-positive patients and 4 paediatric ADA-positive patients developed intermediate ADA responses […]
8). IARs and hypersensitivity reactions may occur independent of the development of ADA. The majority of IARs and hypersensitivity reactions were mild or moderate and were managed with standard clinical practices. IgE ADA testing may be considered for patients who experienced a severe hypersensitivity reaction to olipudase alfa.
While in clinical studies, no loss of efficacy was reported, IgG ADA testing may be considered in case of loss of response to therapy. 8). At the time of the next scheduled infusion, these elevated transaminase levels generally returned to the levels observed prior to the Xenpozyme infusion.
2). During dose escalation or upon resuming treatment following missed doses, transaminases levels should be obtained within 72 hours prior to the next scheduled Xenpozyme infusion. If either the baseline or a pre-infusion transaminase level is > 2 times the ULN during dose escalation, then additional transaminase levels should be obtained within 72 hours after the end of the infusion.
2). Upon reaching the recommended maintenance dose, transaminase testing can be performed as part of routine clinical management of ASMD. 38%, respectively, of the maximum acceptable daily intake of sodium for children below 16 years of age.