Xenpozyme Drug Information
Generic name: OLIPUDASE ALFA-RPCP
Uses of Xenpozyme
is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients. XENPOZYME is a hydrolytic lysosomal sphingomyelin-specific enzyme indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.
Dosage & Administration of Xenpozyme
| First dose (Day 1/Week 0) | 0.1 mg/kg |
|---|---|
| Second dose (Week 2) | 0.3 mg/kg |
| Third dose (Week 4) | 0.3 mg/kg |
| Fourth dose (Week 6) | 0.6 mg/kg |
| Fifth dose (Week 8) | 0.6 mg/kg |
| Sixth dose (Week 10) | 1 mg/kg |
| Seventh dose (Week 12) | 2 mg/kg |
| Eighth dose (Week 14) | 3 mg/kg (recommended maintenance dose) |
Side Effects of Xenpozyme
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. The pooled safety analysis from 3 clinical trials included a total of 38 XENPOZYME-treated patients (30 adult and 8 pediatric patients) with age range from 1.5 to 59 years old receiving intravenous doses up to 3 mg/kg every 2 weeks . The median exposure duration was 2.5 years (range: 0.4 to 3.7 years) in adult patients and 2.7 years (range: 2.5 to 3.2 years) in pediatric patients. Serious adverse reactions of anaphylactic reaction were reported in 2 (25%) XENPOZYME-treated pediatric patients.
Most frequently reported adverse drug reactions in adults (incidence ≥10%) were headache, cough, diarrhea, hypotension, and ocular hyperemia. Most frequently reported adverse drug reactions in pediatric patients (incidence ≥20%) were pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis. Adult patients with ASMD type B and type A/B (Trial 1) In Trial 1, 13 adult patients received XENPOZYME once every 2 weeks for 52 weeks (primary analysis period (PAP)) at dosages escalating from 0.1 mg/kg to a target dose of 3 mg/kg . Adverse reactions that occurred in at least 7% of XENPOZYME-treated adult patients during the PAP are described in Table 7. Table 7: Adverse Reactions Occurring at >7% in Adult Patients with ASMD During the 52-Week Primary Analysis Period in Trial 1 Adverse Reaction XENPOZYME N=13 Placebo N=18 Headache 7 (54%) 8 (44%) Cough 4 (31%) 2 (11%) Diarrhea 2 (15%) 2 (11%) Hypotension 2 (15%) 2 (11%) Ocular hyperemia 2 (15%) 1 (6%) Erythema 1 (8%) 1 (6%) Asthenia 1 (8%) 1 (6%) Pharyngitis 1 (8%) 1 (6%) Dyspnea 1 (8%) 0 Urticaria 1 (8%) 0 Papule 1 (8%) 0 Myalgia 1 (8%) 0 Throat irritation 1 (8%) 0 C-reactive protein abnormal 1 (8%) 0 Pediatric Patients with ASMD type B and type A/B (Trial 2 and Trial 3) In Trial 2, 8 pediatric patients less than or equal to 17 years of age received XENPOZYME intravenously once every 2 weeks for 64 weeks . After 64 weeks, all pediatric patients entered into Trial 3. Adverse reactions that occurred in at least 13% of pediatric patients are described in Table 8. Table 8: Adverse Reactions Occurring at ≥13% in XENPOZYME-Treated Pediatric Patients with ASMD in Trial 2 Duration of treatment in Trial 2 was 64 weeks.
All patients continued into Trial 3. and Trial 3 for an Overall Observation Period of 2.5 to
Years Adverse Reactions
XENPOZYME N=8 Abdominal pain includes abdominal pain and abdominal pain upper Fatigue includes fatigue and asthenia Rash includes rash and erythema Pyrexia 8 (100%) Cough 6 (75%) Diarrhea 6 (75%) Rhinitis 6 (75%) Abdominal pain 5 (63%) Vomiting 4 (50%) Headache 4 (50%) Urticaria 4 (50%) Nausea 3 (38%) Rash 3 (38%) Arthralgia 3 (38%) Pruritus 2 (25%) Fatigue 2 (25%) Pharyngitis 2 (25%) C-reactive protein increased 1 (13%) Hypotension 1 (13%) Anaphylactic reaction 1 (13%) Hypersensitivity 1 (13%) Infusion site swelling 1 (13%) Tachycardia 1 (13%) Pharyngeal swelling 1 (13%) Treatment related serious adverse reactions, hypersensitivity reactions including anaphylaxis, and IARs occurred within 24 hours of infusion and were observed in a higher percentage of pediatric patients than in adult patients. Laboratory Adverse Reaction Elevated transaminase levels ranging from 3 times to 14 times the upper limit of normal (ULN) were reported in 4 (13%) adults and 1 (13%) pediatric patient during the XENPOZYME dose escalation phase in clinical trials. Immunogenicity: Antidrug Antibody-Associated Adverse Reactions In Trial 1, infusion-associated reactions (including hypersensitivity reactions) occurred in a higher percentage in XENPOZYME-treated patients who developed IgG ADA compared to those who did not develop IgG ADA (73% versus 44%) . In Trial 2, one XENPOZYME-treated pediatric patient (18-months old) experienced an anaphylactic reaction during the sixth infusion and developed IgE ADA and the highest IgG ADA titers (ADA peak titer 1,600) of the patients in this trial.
After treatment discontinuation, XENPOZYME was resumed four months later using a diluted drug solution and a desensitization procedure. One pediatric patient (16-months old) with ASMD type A, treated with a version of olipudase alfa manufactured from a different process, experienced anaphylactic reactions (both during the fifth and sixth infusions) and developed IgG ADA (highest titer 1,600) and IgE ADA .
Warnings & Cautions for Xenpozyme
Hypersensitivity Reactions Including Anaphylaxis Life-threatening hypersensitivity reactions, including anaphylaxis, have been reported
in olipudase alfa-treated patients. One 18-month-old XENPOZYME-treated patient experienced an anaphylactic reaction during the sixth infusion in the dose escalation period in Trial 2 . Additionally, a 16-month-old patient with ASMD type A, treated with a version of olipudase alfa manufactured from a different process, experienced two anaphylactic reactions during the fifth and sixth infusions in the dose escalation period; the patient received an immune tolerance induction therapy prior to treatment. In both of these pediatric patients with anaphylaxis, anti-olipudase alfa-rpcp IgE (IgE ADA) and IgG (IgG ADA) antibodies were detected . Hypersensitivity reactions that were mild to moderate in severity occurred in 10 (33%) XENPOZYME-treated adult patients and 4 (50%) XENPOZYME-treated pediatric patients in clinical trials.
Hypersensitivity reactions in adults included urticaria, pruritus, erythema, rash, rash erythematous, eczema, angioedema, and erythema nodosum. Hypersensitivity reactions in pediatric patients included urticaria, pruritus, rash, erythema, and localized edema . Prior to XENPOZYME administration, consider premedicating with antihistamines, antipyretics, and/or corticosteroids. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during XENPOZYME administration.
If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following a severe hypersensitivity reaction (including anaphylaxis). One patient has been rechallenged using slower infusion rates at a dosage lower than the recommended dosage. In patients with a severe hypersensitivity reaction, a tailored desensitization procedure to XENPOZYME may be considered.
If the decision is made to readminister XENPOZYME, ensure the patient tolerates the infusion. If the patient tolerates the infusion, the dosage (dose and/or the rate) may be increased to reach the recommended dosage. Consider testing for IgE ADA in XENPOZYME-treated patients who experienced severe hypersensitivity reactions, including anaphylaxis.
Testing for antibodies against olipudase alfa-rpcp are available through Genzyme Corporation (at 1-800-745-4447). Consider other clinical laboratory testing such as serum tryptase and complement activation in patients who experience anaphylaxis. If a mild or moderate hypersensitivity reaction occurs, consider temporarily holding the infusion, slowing the infusion rate, and/or reducing the XENPOZYME dose .
Infusion-Associated Reactions
IARs occurred in approximately 75% of pediatric and 50% of adult XENPOZYME-treated patients in the clinical trials; a severe IAR occurred in one (12.5%) of the pediatric patients. The most frequent IARs in: ≥10% of adult patients were headache, pruritus, vomiting, and urticaria >20% of pediatric patients were urticaria, erythema, headache, nausea, pyrexia, and vomiting Acute phase reaction (APR), an acute inflammatory response accompanied by elevations in inflammatory serum protein concentrations, was observed in one XENPOZYME-treated adult and one XENPOZYME-treated pediatric patient. Most of the APRs occurred at 48 hours post infusion during the dose escalation period.
Elevations of C-reactive protein, calcitonin, and IL-6, and reduction of serum iron were observed. The most common clinical symptoms associated with APRs were pyrexia, vomiting, and diarrhea. Acute phase reactions were managed similar to other IARs.
In the postmarketing setting, 24 hours after receiving XENPOZYME at a higher than recommended initial dose, a 2-year-old male patient with ASMD, experienced fever, respiratory distress, hypotension, and death . Prior to XENPOZYME administration, consider pre-medicating with antihistamines, antipyretics, and/or corticosteroids to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur in patients after receiving pre-treatment. Follow the dose escalation regimen to minimize IARs . If a severe IAR occurs, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following a severe IAR. One patient has been rechallenged using slower infusion rates at a dosage lower than the recommended dosage.
If the patient tolerates the infusion, the dosage (dose and/or the rate) may be increased to reach the recommended dosage. If a mild or moderate IAR occurs, consider temporarily holding the infusion, slowing the infusion rate, and/or reducing the XENPOZYME dosage .
Elevated Transaminase Levels
XENPOZYME may be associated with elevated transaminases (ALT, AST, or both) within 24 to 48 hours after infusion. Elevated transaminase levels were reported in 4 (13%) XENPOZYME-treated adults and 1 (13%) XENPOZYME-treated pediatric patient during the dose escalation phase in clinical trials. At the time of the next scheduled infusion, these elevated transaminase levels generally returned to levels observed prior to the XENPOZYME infusion . To manage the risk of elevated transaminase levels, assess ALT and AST within one month prior to initiation of XENPOZYME, within 72 hours prior to any infusion during dose escalation, which includes the first 3 mg/kg dose outlined in Tables 1 and 2, or prior to the next scheduled XENPOZYME infusion upon resuming treatment following a missed dose.
If either the baseline or pre-infusion transaminase level (during the dose escalation phase) is >2 times the ULN, repeat transaminase levels within 72 hours after the end of the infusion. If the pre-infusion transaminase levels are elevated above baseline and >2 times the ULN prior to the next scheduled administration, the XENPOZYME dose can be reduced (repeat prior lower dose or reduce the dose) or XENPOZYME can be temporarily withheld until the liver transaminases return to the patient's baseline value. Upon reaching the recommended maintenance dose, transaminase testing is recommended to be continued as part of routine clinical management of ASMD.
Risk of Fetal Malformations During Dosage Initiation or Escalation in Pregnancy
There is no evidence that olipudase alfa-rpcp crosses the human placenta. However, published literature reports that early embryonic exposure to a metabolite of sphingomyelin (ceramide) or the S1P receptor modulator fingolimod can produce exencephaly in chicks and mice, respectively. In animal reproduction studies, exencephaly, a neural tube defect occurring in the first trimester of pregnancy, was observed in mouse fetuses at exposures less than the exposure at the maximum recommended human dose of olipudase alfa-rpcp.
XENPOZYME dosage initiation or escalation, at any time during pregnancy, is not recommended as it may lead to elevated sphingomyelin metabolite levels that may increase the risk of fetal malformations . The decision to continue or discontinue XENPOZYME maintenance dosing in pregnancy should consider the female's need for XENPOZYME, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal ASMD disease. Verify the pregnancy status in females of reproductive potential prior to initiating XENPOZYME treatment. Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if XENPOZYME is discontinued .
Pregnancy Safety for Xenpozyme
Pregnancy Risk Summary Based on findings from animal reproduction studies, XENPOZYME may cause embryo-fetal harm when administered to a pregnant female. XENPOZYME dosage initiation or escalation, at any time during pregnancy, is not recommended as it may lead to elevated sphingomyelin metabolite levels that may increase the risk of fetal malformations (see Data ), . However, the decision to continue or discontinue XENPOZYME maintenance dosing in pregnancy should consider the female's need for XENPOZYME, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal ASMD disease. In an embryo-fetal toxicity study in pregnant mice, a rare malformation (exencephaly) was observed in offspring at an exposure less than the exposure at the maximum recommended human dose (MRHD) of olipudase alfa-rpcp (see Data ). There are no available data on XENPOZYME use in pregnant females to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Advise the pregnant female of the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study in pregnant mice, olipudase alfa-rpcp was administered intravenously at doses of 3, 10, or 30 mg/kg daily from gestation day (GD) 6 through GD 15. Exencephaly was observed in 1 litter at each of the 10 and 30 mg/kg dose groups (2 and 3 fetuses, respectively). These data are consistent with published literature reports that brief embryonic exposures to sphingomyelin metabolites or a sphingosine-1-phosphate (S1P) receptor modulator produced neural tube defects, including exencephaly, in chicks and mice. The developmental No Observed Adverse Effect Level (NOAEL) is 3 mg/kg.
The AUC associated with this dose is 0.14-fold the clinical exposure at the MRHD. The developmental Lowest-Observed-Adverse-Effect Level (LOAEL), 10 mg/kg, is also associated with an exposure that is less than the clinical exposure at the MRHD. In an embryo-fetal development study in pregnant rabbits, olipudase alfa-rpcp was administered intravenously at doses of 3, 10, or 30 mg/kg daily from GD 6 through GD 19. There was no maternal or developmental toxicity. The developmental NOAEL was 30 mg/kg; the AUC 0–24 at this dose is approximately 10.5-fold the exposure at the MRHD. In a study of pre- and postnatal development in mice, olipudase alfa-rpcp was administered intravenously every other day from GD 6 through GD 18; then resumed every other day after parturition, from Lactation Day (LD) 1 through LD 19. Olipudase alfa-rpcp did not induce any effect on maternal reproductive function or on developmental and reproductive parameters of male and female offspring. Therefore, the maternal and developmental NOAELs are 30 mg/kg.
Exposures at this dose, based on the embryo-fetal development study, were estimated to be approximately 1.5-fold the MRHD of olipudase alfa-rpcp.
Pediatric Use of Xenpozyme
Pediatric Use The safety and effectiveness of XENPOZYME for the treatment of non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) have been established in pediatric patients down to birth. Use of XENPOZYME for this indication is supported by evidence from an adequate, and well-controlled trial (Trial 1) in adults with supportive efficacy, safety, and tolerability data in pediatric patients (Trial 2 and Trial 3) . Compared to adults, a higher percentage of pediatric patients experienced treatment related serious adverse reactions, anaphylaxis, hypersensitivity reactions, and IARs that occurred within 24 hours of infusion . Two pediatric patients, an 18 month old receiving XENPOZYME and a 16 month old with ASMD type A that received a version of olipudase alfa manufactured from a different process developed anaphylaxis .
Overdosage Information for Xenpozyme
Cases of overdosage with XENPOZYME have been reported in pediatric patients during dose escalation. Some patients experienced serious adverse reactions including death within 24 hours of initial dose . The clinical findings included fever, hypotension, gastrointestinal bleeding, marked elevation in liver tests, metabolic acidosis, respiratory failure, and vomiting. There is no known specific antidote for XENPOZYME overdosage.
In the event of overdosage, immediately stop the infusion, and monitor the patient closely in a hospital setting for the development of hypersensitivity reactions and IARs including acute phase reactions. For the management of adverse reactions, see Warnings and Precautions and Adverse Reactions .
Clinical Studies of Xenpozyme
Overview of Clinical Trials
The efficacy of XENPOZYME for the treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) has been evaluated in 3 clinical trials involving a total of 61 patients with ASMD: Trial 1 in adult patients (NCT02004691), Trial 2 in pediatric patients (NCT02292654), and Trial 3 a long-term trial in pediatric patients (NCT02004704).
Clinical Trial in Adult Patients with
ASMD Trial 1 was a multicenter, randomized, double-blinded, placebo-controlled, repeat-dose phase II/III trial in adult patients with ASMD (clinical diagnosis consistent with ASMD type B and A/B). In this trial, patients received either XENPOZYME or placebo. Treatment was administered in both groups as an intravenous infusion once every 2 weeks. XENPOZYME was dosed as follows: 0.1 mg/kg (Day 1, Week 0), 0.3 mg/kg (Weeks 2 and 4), 0.6 mg/kg (Weeks 6 and 8), 1 mg/kg (Week 10), 2 mg/kg (Week 12), and then a maintenance dose of 3 mg/kg (Week 14 onwards). The trial was divided into 2 consecutive periods: a randomized 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 randomized to the placebo arm in the PAP crossed over to receive XENPOZYME 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 trial had a diffusion capacity of the lungs for carbon monoxide (DLco) ≤70% of the predicted normal value and a spleen volume ≥6 multiples of normal (MN) measured by magnetic resonance imaging (MRI). The trial population included 87% White, 7% Asian, and 7% other; for ethnicity, 32% identified as Hispanic/Latino, 65% as non-Hispanic/Latino, and 3% were not reported. Five males and 13 females with a median age of 34 years (range: 18 to 66) were included in the placebo arm and 8 males and 5 females with a median age of 34 years (range: 20 to 59) were included in the XENPOZYME arm.
The XENPOZYME and placebo groups included 1 patient (8%) and 2 patients (11%) with mild renal impairment (60 mL/minute ≤ creatinine clearance <90 mL/minute), respectively. There were no patients with moderate or severe renal impairment. Key efficacy endpoints included assessment of % predicted DLco, spleen volume, liver volume, and platelet count.
At Week 52 during the PAP, an increase of 21% in the mean percent change in % predicted DLco was observed in the XENPOZYME-treated patients compared to the placebo-treated patients (Table 9). A reduction in spleen volume of 39% was observed in the XENPOZYME-treated patients compared to the placebo-treated patients. The changes in % predicted DLco and spleen volume were noted at Week 26 of treatment, the first post-dose endpoint assessment (Figures 1 and 2). A decrease in mean liver volume and an increase in mean platelet count were noted in the XENPOZYME-treated patients compared to the placebo-treated patients at Week 52 (Table 9). Table 9: Observed Value and Percentage Change from Baseline to Week 52 in Key Endpoints in Adult Patients with ASMD Type B, A/B on XENPOZYME or Placebo (Trial 1) Placebo XENPOZYME Difference Nominal p value: DLco n 18 13 Mean % predicted DLco at baseline (SD) 48.5
NA n 17 12 Mean % predicted DLco at Week 52 (SD)
49.9
NA n 17 12 LS Mean Percent change in % predicted DLco
at Week 52 (SE) 3.0 23.9 20.9 p value = 0.0003; Spleen volume n 18 13 Mean Spleen Volume (MN) at baseline (SD) 11.2
NA n 17 13 Mean Spleen Volume (MN) at Week 52 (SD)
11.2
NA n 17 13 LS Mean Percent change in Spleen Volume (in
MN) at Week 52 (SE) 0.5 -38.9 -39.4 p value <0.0001; Liver volume n 18 13 Mean Liver Volume (MN) at baseline (SD) 1.6
NA n 17 12 Mean Liver Volume (MN) at Week 52 (SD)
1.6
NA n 17 12 LS Mean Percent change in Liver Volume from
baseline to Week 52 (SE) -1.8 -26.5 -
Platelet count n 18 13 Mean Platelet Count (10 9 /L) at
baseline (SD) 115.6
NA n 16 13 Mean Platelet Count (10 9 /L) at Week
52 (SD) 120.2
NA n 16 13 LS Mean Percent change in Platelet Count from
baseline to Week 52 (SE) 2.7 18.3 +15.6 p value= 0.0280 Seventeen of 18 patients previously receiving placebo and 13 of 13 patients previously treated with XENPOZYME for 52 weeks (in the PAP) started or continued treatment with XENPOZYME, respectively, for up to 4 years. At Week 104, patients initially randomized to placebo had received XENPOZYME for 52 weeks and demonstrated the following LS mean (SE) percent changes in clinical parameters from baseline (before first administration of XENPOZYME): increase in % predicted DLco was 26.8% (Figure 1); reduction in spleen volume (MN) was 36.5% (Figure 2); reduction in liver volume (MN) was 29.5 ; and increase in platelet count was 19.5. Patients in the previous XENPOZYME group demonstrated improvement from baseline to Week 104 in the following parameters: LS mean (SE) percent increase in % predicted DLco was 34.1% (Figure 1); LS mean (SE) percent reduction in spleen volume (MN) was 48.3 (Figure 2); LS mean (SE) percent reduction in liver volume (MN) was 31.7 ; LS mean (SE) percent increase in platelet count was 24.0. Figure 1: Plot of the LS Means (95% CI) of the Percentage Change in DLco (% predicted) from Baseline to Week 104 in Adult Patients with ASMD (Trial 1) 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 by Week 52 and switched to XENPOZYME thereafter.
Figure 2: Plot of the LS Means (95% CI) of the Percentage Change in Spleen Volume (MN) from Baseline to Week 104 in Patients with ASMD (Trial 1) 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 by Week 52 and switched to XENPOZYME thereafter. Figure 1 Figure 2
Clinical Trial in Pediatric Patients with
ASMD Trial 2 was a multi-center, open-label, repeated-dose trial of XENPOZYME administered intravenously once every 2 weeks (via infusion) for 64 weeks in pediatric patients aged <18 years with a clinical diagnosis consistent with ASMD type B and A/B. Exploratory efficacy endpoints related to organomegaly, pulmonary and liver functions, and linear growth were evaluated at Week 52. XENPOZYME was dosed as follows: 0.03 mg/kg (Day 1, Week 0), 0.1 mg/kg (Weeks 2), 0.3 mg/kg (Weeks 4 and 6), 0.6 mg/kg (Week 8 and 10), 1 mg/kg (Week 12), 2 mg/kg (Week 14), and then a maintenance dose of 3 mg/kg (Week 16 onwards). In Trial 2, 8 patients (7 patients from 2 to <12 years old, and 1 patient <2 years old) received an initial dose of 0.03 mg/kg XENPOZYME and all but one completed the dose escalation up to the maintenance dose of 3 mg/kg within 22 weeks. All patients were White and of non-Hispanic/Latino ethnicity. Patients enrolled in the trial had a spleen volume ≥5 MN measured by MRI. Age of patients treated with XENPOZYME ranged from 1 to 10 years old, with both sexes equally represented.
Treatment with XENPOZYME 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 (Table 10). Table 10: Efficacy Results in XENPOZYME-Treated Pediatric Patients with ASMD (Trial 2) Baseline Values Week 52 Values (n=3) (n=3) Mean % predicted DLco (SD) 48.5
LS Mean Percent change in % predicted DLco* (SE) 45.9 95% CI
-12.5, 104.3 (n=8) (n=8) Mean Spleen Volume (MN) (SD) 18.3 9.50 LS Mean Percent change in Spleen Volume (in MN) (SE) -46.7 95% CI -55.5, -37.9 (n=8) (n=8) Mean Liver Volume (MN) (SD) 2.5
LS Mean Percent change in Liver Volume (in MN) (SE) -38.1 95%
CI -44.1, -32.0 (n=8) (n=7) Mean Platelet Count (10 9 /L) (SD) 136.7
LS Mean Percent change in Platelet Count (SE) 37.6 95% CI 8.5
66.7 (n=8) (n=7) Mean height Z-scores (SD) -1.9 -
Extension Trial in
ASMD Pediatric Patients The 8 pediatric patients 2 to <12 years of age from Trial 2 continued treatment in an open label long term trial (Trial 3) and were treated with XENPOZYME for 2.5 to 3.2 years. Efficacy analyses showed continued improvements in the 3 patients evaluated for % predicted DLco, 6 patients evaluated for platelet counts, and all 8 patients evaluated for spleen and liver volumes, compared to baseline, during the additional 6 months extension. In addition, the height Z-score increased by 1.3 from baseline when evaluated through 24 months of XENPOZYME treatment.
Bone age, as assessed by hand x-ray, was delayed by a mean of 26.4 months at baseline in the 7 pediatric patients enrolled in Trial 2 with a bone age measured at Month 24 in Trial 3. The bone age improved to within a mean of 12 months of the chronological age when assessed at Month 24 in these 7 patients.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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