What is Xenpozyme 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.

What is the active ingredient in Xenpozyme?

Olipudase alfa (Olipudasum alfa)

What pharmaceutical form is Xenpozyme available in?

Xenpozyme: Proszek do sporządzania koncentratu roztworu do infuzji 20 mg (dożylna)

Is Xenpozyme OTC or prescription only?

Xenpozyme requires a doctor's prescription.

What are the side effects of Xenpozyme?

Summary of the safety profile Serious adverse reactions reported in patients treated with Xenpozyme were an event of extrasystoles in the context of a history of cardiomyopathy in 1 (2.5%) 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 disconti

Who should NOT take Xenpozyme?

Life-threatening hypersensitivity (anaphylactic reaction) to olipudase alfa or to any of the excipients listed in section 6.1 (see section 4.4).

Does Xenpozyme interact with other medications?

No drug interaction studies have been performed. Because olipudase alfa is a recombinant human protein, no cytochrome P450 mediated drug-drug interactions are expected.

Can Xenpozyme be used during pregnancy?

Women of childbearing potential Women of childbearing potential are advised to use effective contraception during treatment and for 14 days after the last dose if Xenpozyme is discontinued. Pregnancy There are limited data from the use of olipudase alfa in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Xenpozyme is not recommended during pregnancy and in women of childbearing potential not using effective contraception, unless the potenti

What ATC class does Xenpozyme belong to?

Xenpozyme: ATC A16AB25. ATC is the WHO Anatomical Therapeutic Chemical classification — it groups drugs by organ system and pharmacological mechanism.

Xenpozyme

This information is for educational purposes only. It is not intended as medical advice. Always consult a qualified healthcare professional.

Xenpozyme — Description, Dosage, Side Effects | PillsCard

Pharmacotherapeutic group: Other alimentary tract and metabolism products, Enzymes, ATC code: A16AB25 Mechanism of action Olipudase alfa is a recombinant human acid sphingomyelinase that reduces sphingomyelin (SM) accumulation in organs of patients with Acid Sphingomyelinase Deficiency (ASMD). Clinical efficacy and safety The efficacy of olipudase alfa has been evaluated in 3 clinical studies (ASCEND study in adult patients, ASCEND-Peds study in paediatric patients and an extension study in adult and paediatric patients) involving a total of 61 patients with ASMD. Clinical study in adult patients The ASCEND study is a multicenter, randomised, double-blinded, placebo-controlled, repeat-dose phase II/III study in adult patients with ASMD type A/B and B.‍‍‍‍‍‍‍‍‍‍‍‍‍ A total of 36 patients were randomised in a 1:1 ratio to receive either Xenpozyme or placebo. Treatment was administered in both groups as an intravenous infusion once every 2 weeks. Patients receiving olipudase alfa were up titrated from 0.1 mg/kg to a target dose of 3 mg/kg. The study was divided into 2 consecutive periods: a randomised placebo-controlled, double-blinded primary analysis period (PAP) which lasted to week 52, followed by an extension treatment period (ETP) for up to 4 years. Patients randomised to the placebo arm in the PAP crossed over to active treatment in the ETP to reach the targeted dose of 3 mg/kg, while patients in the original Xenpozyme arm continued treatment. Patients enrolled in the study had a diffusion capacity of the lungs for carbon monoxide (DLco) ≤70% of the predicted normal value, a spleen volume ≥6 multiples of normal (MN) measured by magnetic resonance imaging (MRI) and scores ≥5 in splenomegaly related score (SRS). Overall, demographic and disease characteristics at baseline were similar between the two treatment groups. The median patient age was 30 years (range: 18 – 66 years). The mean (standard deviation, SD) age at ASMD diagnosis was 18 (18.4) years. At baseline, neurologic manifestations were seen in 9 out of 36 adult patients (25%) consistent with a clinical diagnosis of ASMD Type A/B. The remaining 27 patients had a clinical diagnosis consistent with ASMD Type B. This study included 2 separate primary efficacy endpoints: the percentage change in DLco (in % predicted of normal) and spleen volume (in MN), as measured by MRI, from baseline to week 52. Secondary efficacy endpoints included the percentage change in liver volume (in MN) and platelet count from baseline to week 52. Pharmacodynamic parameters (ceramide and lyso-sphingomyelin [a deacylated form of SM] levels) were also assessed. Improvements in mean percent change in % predicted DLco (p= 0.0004) and spleen volume (p< .0001) as well as in mean liver volume (p< .0001) and platelet count (p= 0.0185) were observed in the Xenpozyme group as compared to the placebo group during the 52-week primary analysis period. A significant improvement in mean percent change in % predicted DLco, spleen volume, liver volume and platelet count was noted at week 26 of treatment, the first post-dose endpoint assessment. The results from the PAP at week 52 are detailed in Table 6. Table 6: Mean (SD) values for efficacy endpoints at baseline and least squares (LS) mean percentage change (SE) from baseline to week 52 Placebo (n=18) Xenpozyme (n=18) Difference [95% CI] p value* Primary endpoints Mean % predicted DLco at baseline Percent change in % predicted DLco from baseline to week 52 48.5 (10.8) 3 (3.4) 49.4 (11.0) 22 (3.3) NA 19 (4.8) [9.3, 28.7] NA 0.0004 Mean spleen volume (MN) at baseline Percent change in spleen volume from baseline to week 52 11.2 (3.8) 0.5 (2.5) 11.7 (4.9) -39.4 (2.4) NA -39.9 (3.5) [-47.1, -32.8] NA <0.0001 Secondary endpoints Mean liver volume (MN) at baseline Percent change in liver volume from baseline to week 52 1.6 (0.5) -1.5 (2.5) 1.4 (0.3) -28.1 (2.5) NA -26.6 (3.6) [-33.9, -19.3] NA <0.0001 Mean platelet count (10 9 /L) at baseline Percent change in platelet count from baseline to week 52 115.6 (36.3) 2.5 (4.2) 107.2 (26.9) 16.8 (4.0) NA +14.3 (5.8) [2.6, 26.1] NA 0.0185 *Statistically significant after multiplicity adjustment In addition, lyso-sphingomyelin, which is substantially elevated in plasma of ASMD patients, declined significantly, reflecting reduction of sphingomyelin content in tissue. The LS mean percentage change from baseline to week 52 (SE) in pre-infusion plasma lyso-sphingomyelin level was 77.7 % (3.9) in the Xenpozyme treatment group compared to 5.0% (4.2) in the placebo group. The liver sphingomyelin content, as assessed by histopathology, decreased by 92.0% (SE: 8.1) from baseline to week 52 in the Xenpozyme treatment group (compared to +10.3% (SE: 7.8) in the placebo group). Seventeen of 18 patients previously receiving placebo and 18 of 18 patients previously treated with olipudase alfa for 52 weeks (PAP) started or continued treatment with olipudase alfa, respectively, for up to 4 years. Sustained effects of olipudase alfa on efficacy endpoints up to week 104 are presented in Figures 1 and 2 and Table 7. Figure 1: Plot of the LS means (95%CI) of the percentage change in DLco (% predicted) from baseline to week 104 - mITT population The vertical bars represent the 95% CIs for the LS means. The LS means and 95% CIs are based on a mixed model for repeated measures approach, using data up to week 104. Patients in placebo/Xenpozyme group received placebo up to week 52 and switched to olipudase alfa thereafter. Figure 2: Plot of the LS means (95%CI) of the percentage change in spleen volume (MN) from baseline to week 104 - mITT population The vertical bars represent the 95% CIs for the LS means. The LS means and 95% CIs are based on a mixed model for repeated measures approach, using data up to week 104. Patients in placebo/Xenpozyme group received placebo up to week 52 and switched to olipudase alfa thereafter. Table 7: LS mean percentage change (SE) from baseline to week 104 for liver volume (MN) and platelet count (10 9 /L) in patients treated with olipudase alfa for 104 weeks Previous olipudase alfa group week 52 (ETP start) week 104 N Percent change in liver volume (SD) 17 -27.8 (2.5) 14 -33.4 (2.2) N Percent change in platelet count (SD) 18 16.6 (4.0) 13 24.9 (6.9) N: number of patients Extension study in adult patients Five adult patients who participated in an open-label ascending dose study in ASMD patients continued treatment in an open-label extension study and received olipudase alfa for up to >9 years. Sustained improvements in % predicted DLco, spleen and liver volumes and platelet count, compared to baseline, were noted in adult over the course of the study (see Table 8). Table 8: Mean percentage change (SD) from baseline to month 78 of efficacy parameters Month 78 (N=5) Percent change in % predicted DLco (SD) 55.3% (48.1) Percent change in spleen volume (SD) -59.5% (4.7) Percent change in liver volume (SD) -43.7% (16.7) Percent change in platelet count (SD) 38.5% (14.7) N: number of patients Paediatric population The ASCEND-Peds study (Phase 1/2 clinical study) is a multi-center, open-label, repeated-dose study to evaluate the safety and tolerability of olipudase alfa administered for 64 weeks in paediatric patients aged <18 years with ASMD (type A/B and B). In addition, exploratory efficacy endpoints related to organomegaly, pulmonary and liver functions, and linear growth were evaluated at week 52. A total of 20 patients (4 adolescents from 12 to <18 years old, 9 children from 6 to <12 years old, and 7 infants/ children < 6 years old) were up-titrated with olipudase alfa via a dose escalation regimen from 0.03 mg/kg to a target dose of 3 mg/kg. Treatment was administered as an intravenous infusion once every 2 weeks for up to 64 weeks. Patients enrolled in the study had a spleen volume ≥ 5 MN measured by MRI. Patients were distributed across all ages from 1.5 to 17.5 years old, with both sexes equally represented. The mean (SD) age at ASMD diagnosis was 2.5 (2.5) years. At baseline, neurologic manifestations were seen in 8 out of 20 paediatric patients (40%) consistent with a clinical diagnosis of ASMD Type A/B. The remaining 12 patients had a clinical diagnosis consistent with ASMD Type B. Treatment with olipudase alfa resulted in improvements in mean percent change in % predicted DLco, spleen and liver volumes, platelet counts, and linear growth progression (as measured by Height Z-scores) at week 52 as compared to baseline (see Table 9). Table 9: LS Mean percentage change (SE) or change (SD) from baseline to week 52 (all age cohort) of efficacy parameters Baseline value (n=20) Week 52 (n=20) Mean % predicted DLco (SD) Percent change in % predicted DLco* 95% CI 54.8 (14.2) 71.7 (14.8) 32.9 (8.3) 13.4, 52.5 Mean spleen volume (MN) (SD) Percent change in spleen volume (in MN) 95% CI 19.0 (8.8) 9.3 (3.9) -49.2 (2.0) -53.4, -45.0 Mean liver volume (MN) (SD) Percent change in liver volume (in MN) 95% CI 2.7 (0.7) 1.5 (0.3) -40.6 (1.7) -44.1, -37.1 Mean platelet count (10 9 /L) (SD) Percent change in platelet count 95% CI 137.7 (62.3) 173.6 (60.5) 34.0 (7.6) 17.9, 50.1 Mean height Z-scores (SD) Change in height Z-scores* 95% CI -2.1 (0.8) -1.6 (0.8) 0.6 (0.4) (0.38,0.73) *DLco was evaluated in 9 paediatric patients aged ≥ 5 years who were able to perform the test, change in height Z-score was evaluated in 19 paediatric patients. In addition, LS mean pre-infusion plasma ceramide and lyso-sphingomyelin levels were reduced by 57% (SE: 5.1) and 87.2% (SE: 1.3), respectively, compared to baseline following 52 weeks of treatment. The effects of olipudase alfa on spleen and liver volumes, platelets and height z-scores were seen across all paediatric age cohorts included in the study. Extension study paediatric patients Twenty paediatric patients who participated in ASCEND-Peds study continued treatment in an open-label extension study and received olipudase alfa for up to > 8 years. Sustained improvements in efficacy parameters (% predicted DLco, spleen and liver volumes, platelet counts, height Z-scores and bone age) were noted in paediatric patients over the course of the study up to month 48 (see Table 10). Table 10: Mean percentage change or change (SD) from baseline to month 48 (all age cohort) of efficacy parameters Month 48 N Percent change in % predicted DLco (SD) 5 60.3 (58.5) N Percent change in spleen volume (SD) 7 -69.1 (4.1) N Percent change in liver volume (SD) 7 -55.4 (11.0) N Percent change in platelet count (SD) 5 35.8 (42.4) N Change in height Z-scores (SD) 5 2.3 (0.8) N Change in bone age (months) (SD) 7 18.5 (19.0) N: number of patients

⚠️ Warnings

Vials are for single use only. Infusions should be administered in a stepwise manner preferably using an infusion pump. Preparation of the dosing solution The powder for concentrate for solution for infusion must be reconstituted with sterile water for injection, diluted with sodium chloride 9 mg/mL (0.9%) solution for injection and then administered by intravenous infusion. The reconstitution and dilution steps must be completed under aseptic conditions.‍‍‍‍‍‍‍‍‍‍‍‍‍ Filtering devices should not be used at any time during the preparation of the infusion solution. Avoid foaming during reconstitution and dilution steps. 1) Determine the number of vials to be reconstituted based on the individual patient's weight and the prescribed dose. Patient weight (kg) × dose (mg/kg) = patient dose (in mg). Patient dose (in mg) divided by 20 mg/vial = number of vials to reconstitute. If the number of vials includes a fraction, round up to the next whole number. 2) Remove the required number of vials from refrigeration and set aside for approximately 20 to 30 minutes to allow them to reach room temperature. 3) Reconstitute each vial by injecting 5.1 mL of sterile water for injection into the vial using a slow drop-wise addition technique to the inside wall of the vial. 4) Tilt and roll each vial gently. Each vial will yield a 4 mg/mL clear, colorless solution. 5) Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. Xenpozyme solution should be clear and colorless. Any vials exhibiting opaque particles or discoloration should not be used. 6) Withdraw the volume of reconstituted solution, corresponding to the prescribed dose, from the appropriate number of vials and dilute with sodium chloride 9 mg/mL (0.9%) solution for injection, in a syringe or infusion bag depending on the volume of infusion (see Table 12 for the recommended total infusion volume based on patients age and/or weight). Table 12: Recommended infusion volumes Body weight ≥3 kg to <10 kg Body weight ≥10 kg to <20 kg Body weight ≥20 kg (paediatric patients <18 years) Adult patients (≥18 years) Dose (mg/kg) Total infusion volume (mL) Total infusion volume (mL) Total infusion volume (mL) Total infusion volume (mL) 0.03 Variable volume will vary based on body weight Variable volume will vary based on body weight 5 NA 0.1 Variable volume will vary based on body weight 5 10 20 0.3 5 10 20 100 0.6 10 20 50 100 1 20 50 100 100 2 50 75 200 100 3 50 100 250 100 • For variable final volumes of infusion based on body weight in paediatric patients (see Table 12): - Prepare an infusion solution at 0.1 mg/mL by adding 0.25 mL (1 mg) of the reconstituted solution prepared in step 3) and 9.75 mL of sodium chloride 9 mg/mL (0.9%) solution for injection in an empty 10 mL syringe. - Calculate the volume (mL) required to obtain the patient dose (mg). Example: 0.3 mg ÷ 0.1 mg/mL = 3 mL • Dilution instructions for 5 mL ≤ total volume ≤20 mL using a syringe: - Inject the required volume of the reconstituted solution slowly to the inside wall of the empty syringe. - Add slowly the sufficient quantity of sodium chloride 9 mg/mL (0.9%) solution for injection to obtain the required total infusion volume (avoid foaming within the syringe). • Dilution instructions for a total volume ≥50 mL using an infusion bag: - Empty infusion bag: o Inject slowly the required volume of the reconstituted solution from step 3) in the appropriate size sterile infusion bag. o Add slowly the sufficient quantity of sodium chloride 9 mg/mL (0.9%) solution for injection to obtain the required total infusion volume (avoid foaming within the bag). - Pre-filled infusion bag: o Withdraw from the infusion bag pre-filled with sodium chloride 9 mg/mL (0.9%) solution for injection the volume of normal saline to obtain a final volume as specified in Table 12. o Add slowly the required volume of the reconstituted solution from step 3) into the infusion bag (avoid foaming within the bag). 7) Gently invert the syringe or the infusion bag to mix. Do not shake. Because this is a protein solution, slight flocculation (described as thin translucent fibers) occurs occasionally after dilution. 8) The diluted solution must be filtered through an in-line low protein-binding 0.2 μm filter during administration. 9) After the infusion is complete, the infusion line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection using the same infusion rate as the one used for the last part of the infusion. Disposal Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Xenpozyme

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