XENPOZYME™ (olipudase alfa-rpcp) for ASMD treatment (non-CNS manifestations)
Important Safety Information Prescribing Information For Healthcare Professionals
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THE FIRST AND ONLY DISEASE-SPECIFIC TREATMENT FOR ASMD (NON-CNS MANIFESTATIONS)

XENPOZYME (olipudase alfa-rpcp) is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.
Prescribing Information including Boxed WARNING

CNS=central nervous system.

WHAT IS ASMD?

ASMD is an inherited condition with multiorgan symptoms that can worsen over time

  • Historically known as Niemann-Pick disease types A, A/B, and B, ASMD is caused by reduced activity of an enzyme called acid sphingomyelinase (ASM).
  • When you have this ASM enzyme deficiency, your body cannot adequately break down a substance in your cells called sphingomyelin. This may lead to a buildup of sphingomyelin in certain organs, such as the lungs, spleen, and liver.

Over time, ASMD can lead to multiorgan symptoms including:

lungs icon
Decreased lung function
liver icon liver icon
Enlarged liver and/or spleen
platelet count icon
Low platelet count, which can lead to easy bleeding and bruising
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Growth delay in children
XENPOZYME OVERVIEW

The first and only disease-specific treatment for ASMD (non-CNS manifestations)

XENPOZYME is an enzyme replacement therapy that provides the ASM enzyme that is deficient in people with ASMD. XENPOZYME does not impact symptoms related to the central nervous system.
The effectiveness of XENPOZYME has been evaluated in 3 clinical trials including adults and children with ASMD.
The safety of XENPOZYME has been evaluated across 3 clinical trials including adults and children with ASMD.
XENPOZYME is administered in 2 phases, dose escalation followed by maintenance, with a potential option of home infusion during the maintenance phase. The decision to move to home infusion can only be made after evaluation and recommendation by your prescribing doctor.

How does XENPOZYME work?

XENPOZYME provides the enzyme that is deficient or missing, helping to reduce the buildup of a substance called sphingomyelin in cells. XENPOZYME does not impact symptoms related to the central nervous system.
Healthy cell with no sphingomyelin buildup. ASMD causes sphingomyelin buildup in cells. XENPOZYME™ (olipudase alfa-rpcp) replaces the ASM enzyme and helps reduce the buildup of sphingomyelin.
Healthy cell
ASMD causes a buildup of sphingomyelin in the cells.
XENPOZYME replaces the ASM enzyme and helps reduce the buildup of sphingomyelin.
Lysosome, accumulated sphingomyelin, ASM enzyme, & ASM replacement XENPOZYME™ (olipudase alfa-rpcp).
Healthy cell with no sphingomyelin buildup. Healthy cell
ASMD causes sphingomyelin buildup in cells. ASMD causes a buildup of sphingomyelin in the cells.
XENPOZYME™ (olipudase alfa-rpcp) replaces the ASM enzyme and helps reduce the buildup of sphingomyelin. XENPOZYME replaces the ASM enzyme and helps reduce the buildup of sphingomyelin.
Lysosome, accumulated sphingomyelin, ASM enzyme, & ASM replacement XENPOZYME™ (olipudase alfa-rpcp).
ABOUT XENPOZYME

XENPOZYME demonstrated improvement across multiple organs in adults

A clinical trial in adults
  • Evaluated the safety and effectiveness of XENPOZYME in 31 adults with ASMD type B or type A/B, 18 to 66 years of age.
  • Randomized treatment: 13 adults received XENPOZYME and the other 18 adults received placebo. The clinical trial was blinded, meaning the participants and their doctors did not know if they were taking placebo or taking XENPOZYME.
  • Followed all adults over 1 year, after which time those receiving placebo were offered XENPOZYME, and all were offered the option to remain in the trial for up to 4 years.
  • 17 of 18 adults previously receiving placebo and 13 of 13 adults previously treated with XENPOZYME for 52 weeks started or continued treatment with XENPOZYME, respectively, for up to 4 years.
After 1 year of treatment, adults taking XENPOZYME experienced improvement in the following endpoints: XENPOZYME™ (olipudase alfa-rpcp) adult data on lung function (DLco), spleen volume, liver volume, & platelet count. XENPOZYME™ (olipudase alfa-rpcp) adult data on lung function (DLco), spleen volume, liver volume, & platelet count.

*The clinical trial studied the percentage change in lung function as measured by DLco from baseline to Week 52.

DLco=diffusing capacity of the lungs for carbon monoxide; MN=multiples of normal.

XENPOZYME safety profile in adults The safety of XENPOZYME was evaluated in the clinical trial over 1 year Adverse events that occurred in at least 1 adult treated with XENPOZYME
ADVERSE REACTION XENPOZYME (N=13) PLACEBO (N=18)
Headache 7 (54%) 8 (44%)
Cough 4 (31%) 2 (11%)
Diarrhea 2 (15%) 2 (11%)
Low blood pressure 2 (15%) 2 (11%)
Eye redness 2 (15%) 1 (6%)
Skin rednesss 1 (8%) 1 (6%)
Weakness/fatigue 1 (8%) 1 (6%)
Sore throat 1 (8%) 1 (6%)
Shortness of breath 1 (8%) 0
Hives 1 (8%) 0
Skin lesions 1 (8%) 0
Muscle pain 1 (8%) 0
Throat irritation 1 (8%) 0
C-reactive protein abnormal 1 (8%) 0
  • The most frequently reported adverse drug reactions in adults (incidence ≥10%) were headache, cough, diarrhea, low blood pressure, and eye redness.
XENPOZYME demonstrated improvement across multiple organs in children
A clinical trial in children
  • Evaluated the safety and effectiveness of XENPOZYME in children with ASMD type B or type A/B <18 years old over 64 weeks.
  • Included 8 children (7 children from 2 to <12 years old, and 1 child <2 years old) who all received XENPOZYME.
After 1 year of treatment, children taking XENPOZYME experienced improvement in the following exploratory endpoints: XENPOZYME pediatric data on lung function, spleen volume, liver volume, platelet count, height.
XENPOZYME pediatric data on lung function, spleen volume, liver volume, platelet count, height.

The clinical trial studied the percentage change in lung function as measured by DLco from baseline to Week 52.

In children, XENPOZYME demonstrated improvements in a Long-Term Trial

  • 8 children from the clinical trial continued treatment in a Long-Term Trial.
  • Upon entering the trial, the 8 children ranged in age from 2 to <12 years and were treated for 2.5 to 3.2 years.
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Long-Term Trial results
  • Improvements continued in the 3 children evaluated for % predicted DLco, in the 8 children evaluated for spleen and liver volumes, and in the 6 children evaluated for platelet count during the additional 6 months of the trial.
  • 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, which was delayed by a mean of 26 months at baseline in the 7 children enrolled in the clinical trial, improved to within a mean of 12 months of the chronological age when assessed at Month 24 in all 7 children who were enrolled in the Long-Term Trial.
XENPOZYME safety profile in children

The safety of XENPOZYME was evaluated in the clinical trial over 64 weeks and in the Long-Term Trial for an overall observation period up to 3.2 years

Adverse events that occurred in at least 1 child treated with XENPOZYME
ADVERSE REACTION XENPOZYME (N=8)
Fever 8 (100%)
Cough 6 (75%)
Diarrhea 6 (75%)
Stuffy nose 6 (75%)
Stomach pain 5 (63%)
Vomiting 4 (50%)
Headache 4 (50%)
Hives 4 (50%)
Nausea 3 (38%)
Rash 3 (38%)
Joint pain 3 (38%)
Itch 2 (25%)
Fatigue 2 (25%)
Sore throat 2 (25%)
C-reactive protein increased 1 (13%)
Low blood pressure 1 (13%)
Anaphylactic reaction 1 (13%)
Hypersensitivity 1 (13%)
Infusion site swelling 1 (13%)
Irregular heartbeat 1 (13%)
Throat irritation/swelling 1 (13%)
  • The most frequently reported adverse drug reactions in children (incidence >20%) were fever, cough, diarrhea, stuffy nose, vomiting, stomach pain, headache, hives, nausea, rash, joint pain, itch, fatigue, and sore throat.
  • Serious anaphylactic reactions were reported in 2 (25%) children treated with XENPOZYME.
  • Treatment-related serious adverse reactions, hypersensitivity reactions (including anaphylaxis), and infusion-associated reactions (IARs) occurred within 24 hours of infusion and were observed in a higher percentage of children than in adults.
For adults and children with ASMD: What to look for when taking XENPOZYME
  • Some people experienced mild, moderate, or severe hypersensitivity reactions with XENPOZYME, meaning their immune systems had an exaggerated response to the medication such as developing hives, redness to the skin, or itchy skin. The doctor might consider pretreatment with other medications to lessen the chance of a hypersensitivity reaction. The doctor will also monitor you or your child and will be prepared to follow the appropriate course of action if a reaction occurs.
  • XENPOZYME is given as an intravenous infusion. Some people experienced side effects in the clinical trials that may have been associated with the XENPOZYME infusion. These are called IARs and they typically occurred between the time of infusion and up to 24 hours after the infusion was complete.
  • If you or your child is having a reaction to the infusion, whether mild or severe, tell the doctor or infusion nurse right away. The doctor may slow or stop the infusion and may lower the next dose.
  • IARs occurred in approximately 50% of adults taking XENPOZYME.
  • IARs occurred in approximately 75% of children taking XENPOZYME. A severe IAR occurred in 1 child (12.5%).
icon 1 IN THE CLINICAL TRIALS, THE MAJORITY OF IARs WITH XENPOZYME WERE MILD TO MODERATE
icon 2 DURING THE INFUSION, THE DOCTOR WILL MONITOR FOR IARs
icon 3 THE MOST FREQUENT IARs IN ADULTS (≥10%) WERE HEADACHE, ITCHING, VOMITING, AND HIVES
icon 4 THE MOST FREQUENT IARs IN CHILDREN (>20%) WERE HIVES, RASH, HEADACHE, NAUSEA, FEVER, AND VOMITING
STARTING XENPOZYME
How to take XENPOZYME
  • XENPOZYME is given as an intravenous infusion once every 2 weeks—the dose is based on body weight.
  • XENPOZYME must always be administered by a trained healthcare provider.
Before initiating XENPOZYME
  • XENPOZYME dosage initiation or escalation, at any time during pregnancy, is not recommended. Based on findings from animal studies, treatment with XENPOZYME may cause defects in the fetus.
  • If you are a female of reproductive potential, your doctor will verify your pregnancy status before starting treatment with XENPOZYME.
  • Use effective contraception during treatment with XENPOZYME and for 14 days after the last dose if XENPOZYME is discontinued.
  • If you are pregnant or plan to become pregnant, tell your doctor right away.
  • Your doctor will order a baseline liver enzyme level measurement for you or your child within 1 month prior to the start of treatment.
  • Prior to infusion, your doctor may decide to pretreat you or your child with anti-fever, anti-allergy, and/or steroid medications.
XENPOZYME dosing First phase is called dose escalation You or your child will start on a low dose that will gradually increase at every infusion. This will last at least 14 weeks for adults and at least 16 weeks for children.
dose escalation Why dose escalation? Gradual dose escalation is essential and may reduce the risk of IARs and elevated liver enzyme levels when first starting treatment.
hospital icon Where does dose escalation take place? The dose escalation period takes place in a clinical setting to manage for the possibility of severe reactions.

In clinical trials, all but 1 of the pediatric patients completed the dose escalation up to the target maintenance dose of 3 mg/kg within 22 weeks.

Second phase is called maintenance After dose escalation, the target maintenance dose is 3 mg/kg.
arrow right icon Why ongoing maintenance? In people with ASMD, the body is unable to make enough of the ASM enzyme; therefore, it is important to keep taking XENPOZYME every 2 weeks.
infusion icon Can infusions take place at home? Once you or your child starts receiving the maintenance dose, there is a potential option of receiving XENPOZYME at home if the doctor recommends it.
Dosing for adults XENPOZYME™ (olipudase alfa-rpcp) dosing information for adult patients. XENPOZYME™ (olipudase alfa-rpcp) dosing information for adult patients.
Dosing for children XENPOZYME™ (olipudase alfa-rpcp) dosing information for pediatric patients. XENPOZYME™ (olipudase alfa-rpcp) dosing information for pediatric patients.

In clinical trials, all but 1 of the pediatric patients completed dose escalation up to the target maintenance dose of 3 mg/kg within 22 weeks.

What else do I need to know?

  • During the infusion, the doctor or infusion nurse will monitor for IARs. If you or your child experiences an IAR, the doctor may stop the infusion, slow the infusion, or lower the infusion dose.
  • During dose escalation, the doctor will regularly order blood tests to monitor how the liver is working because some people experienced a temporary increase in liver enzymes during the clinical trials. If liver enzymes are elevated during dose escalation, the doctor may delay an infusion, repeat a dose, or lower the dose for the next infusion.
  • During the maintenance phase, upon reaching the recommended target maintenance dose, testing for liver enzyme levels is recommended to be continued as part of routine clinical management of ASMD.
missed infusion icon
Missed infusions
Be sure to keep all your infusion appointments. If 3 or more doses are missed, you or your child will need to return to dose escalation. Dose escalation should take place in a clinical setting.
SUPPORT & RESOURCES
CareConnectPSS® provides personalized support services to people with ASMD. From diagnosis and treatment journey to insurance coverage and community connections, CareConnectPSS has someone available to help.
treatment icon
SPEAKING ASMD ASMD can be hard to understand or explain. CareConnectPSS offers disease and treatment education—both in–person and virtually—for you, family members, and important members of your community.
transition of care icon
INSURANCE COVERAGE It is important to understand insurance coverage. CareConnectPSS has experts to help you navigate the healthcare system so you can access your benefits and know your options.
insurance icon
CARE COORDINATION It is important to stay connected to ASMD healthcare providers. We can assist you in finding medical facilities with ASMD specialists. If you relocate or travel, CareConnectPSS can also help with logistics.
resource connections icon
FINANCIAL ASSISTANCE When it comes to ASMD, you are not alone. CareConnectPSS can help you understand and manage treatment costs, follow up on insurance claims, and find assistance programs.
SPEAKING ASMD treatment icon ASMD can be hard to understand or explain. CareConnectPSS offers disease and treatment education—both in–person and virtually—for you, family members, and important members of your community.
CARE COORDINATION insurance icon It is important to stay connected to ASMD healthcare providers. We can assist you in finding medical facilities with ASMD specialists. If you relocate or travel, CareConnectPSS can also help with logistics.
INSURANCE COVERAGE transition of care icon It is important to understand insurance coverage. CareConnectPSS has experts to help you navigate the healthcare system so you can access your benefits and know your options.
FINANCIAL ASSISTANCE resource connections icon When it comes to ASMD, you are not alone. CareConnectPSS can help you understand and manage treatment costs, follow up on insurance claims, and find assistance programs.
Access personalized support and resources at CareConnectPSS.com.
Services are also available at 1-800-745-4447 (toll free), Option 3, or email Info@CareConnectPSS.com.
Access personalized support and resources at CareConnectPSS.com.
Services are also available at
1-800-745-4447
(toll free),
Option 3, or email Info@CareConnectPSS.com.
Downloadable resources

Patient at Home Infusion Guide

A detailed guide for transitioning XENPOZYME infusions to the home setting.

DOWNLOAD

Patient Discussion Guide

A guide to help facilitate XENPOZYME treatment discussions with your doctor.

DOWNLOAD

Adherence Flashcard

An informative flashcard that can help you stay on track with XENPOZYME.

DOWNLOAD

Patient Dosing Guide

A detailed guide to understanding dosing and administration with XENPOZYME.

DOWNLOAD

Patient Brochure

A helpful brochure that provides a comprehensive overview of XENPOZYME treatment.

DOWNLOAD
IMPORTANT SAFETY INFORMATION
WARNING: SEVERE HYPERSENSITIVITY REACTIONS
Hypersensitivity Reactions Including Anaphylaxis
Hypersensitivity reactions, including severe reactions known as anaphylaxis, may occur during and after XENPOZYME treatment. You should seek immediate medical care if hypersensitivity reactions (including anaphylaxis) occur. If a severe hypersensitivity reaction occurs, your doctor may decide to discontinue XENPOZYME immediately and provide appropriate medical care. Appropriate medical support measures may be administered, and you may require close observation during and after XENPOZYME administration.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis
Your doctor may decide to give you antihistamine, anti-fever, and/or steroid medications before your infusions.
  • If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, your doctor should discontinue XENPOZYME immediately and initiate appropriate medical treatment.
  • If a mild or moderate hypersensitivity reaction occurs, your doctor may adjust or temporarily withhold your infusion rate or dose of XENPOZYME.

Hypersensitivity reactions, including anaphylaxis, have been reported in olipudase alfa-treated patients.
  • Signs of hypersensitivity reactions in adults included hives, itchy skin, skin redness, rash, swelling underneath the skin, and tender bumps under the skin.
  • Hypersensitivity reactions in pediatric patients included hives, itchy skin, rash, and localized swelling.

Infusion-Associated Reactions
Your doctor may decide to give you antihistamine, anti-fever, and/or steroid medications before your infusions to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur after receiving these medications.
  • If severe IARs occur, your doctor should discontinue XENPOZYME immediately and initiate appropriate medical treatment.
  • If a mild or moderate IAR occurs, your doctor may adjust or temporarily withhold your infusion rate or dose of XENPOZYME.

The most frequent IARs in:
  • adult patients were headache, rash, vomiting, and hives;
  • pediatric patients were hives, swelling, headache, nausea, fever, and vomiting.

An acute phase reaction (APR), an acute inflammatory response accompanied by elevations in inflammatory protein concentrations from blood tests, was observed.
  • Most of the APRs occurred at 48 hours post infusion during the dose escalation period.
  • The most common symptoms of APRs were fever, vomiting, and diarrhea.
  • Your doctor can manage APRs like other IARs you may experience.

Elevated Transaminases Levels
XENPOZYME may be associated with elevated liver enzymes, known as transaminases, within 24 to 48 hours after infusion.
  • Elevated transaminase levels were reported in patients during the XENPOZYME dose escalation phase in clinical trials.

To manage the risk of elevated transaminase levels, your doctor should check your liver enzyme levels with a blood test:
  • within one month before starting XENPOZYME;
  • within 72 hours before any infusion during the dose escalation phase, or before your next scheduled XENPOZYME infusion if you missed a dose.

Based on the levels of transaminases from your blood tests, your doctor may make changes to your dose or infusion schedule.
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
XENPOZYME dosage initiation or escalation, for a female at any time during her pregnancy, is not recommended as it may increase risk of defects in the fetus. The decision to continue or discontinue XENPOZYME maintenance dosing, if you are a pregnant female, should be determined by you and your doctor and should consider your need for XENPOZYME, the potential drug-related risks to the fetus, and the potential risks due to untreated maternal ASMD disease.
If you are a female of reproductive potential, your doctor will verify your pregnancy status before you start treatment with XENPOZYME. You should use effective contraception during XENPOZYME treatment and for 14 days after your last dose if XENPOZYME is discontinued.
ADVERSE REACTIONS
  • Most frequently reported adverse drug reactions in adults (incidence ≥10%) were headache, cough, diarrhea, low blood pressure, and redness in the eye.
  • Most frequently reported adverse drug reactions in pediatric patients (incidence ≥20%) were fever, cough, diarrhea, runny nose, abdominal pain, vomiting, headache, hives, nausea, rash, joint pain, itchy skin, fatigue, and sore throat.

INDICATIONS AND USAGE
XENPOZYME (olipudase alfa-rpcp) is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.
Please see full Prescribing Information, including Boxed WARNING, for complete details.
isi open button
IMPORTANT SAFETY INFORMATION
WARNING: SEVERE HYPERSENSITIVITY REACTIONS
Hypersensitivity Reactions Including Anaphylaxis
Hypersensitivity reactions, including severe reactions known as anaphylaxis, may occur during and after XENPOZYME treatment. You should seek immediate medical care if hypersensitivity reactions (including anaphylaxis) occur. If a severe hypersensitivity reaction occurs, your doctor may decide to discontinue XENPOZYME immediately and provide appropriate medical care. Appropriate medical support measures may be administered, and you may require close observation during and after XENPOZYME administration.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions Including Anaphylaxis
Your doctor may decide to give you antihistamine, anti-fever, and/or steroid medications before your infusions.
  • If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, your doctor should discontinue XENPOZYME immediately and initiate appropriate medical treatment.
  • If a mild or moderate hypersensitivity reaction occurs, your doctor may adjust or temporarily withhold your infusion rate or dose of XENPOZYME.

Hypersensitivity reactions, including anaphylaxis, have been reported in olipudase alfa-treated patients.
  • Signs of hypersensitivity reactions in adults included hives, itchy skin, skin redness, rash, swelling underneath the skin, and tender bumps under the skin.
  • Hypersensitivity reactions in pediatric patients included hives, itchy skin, rash, and localized swelling.

Infusion-Associated Reactions
Your doctor may decide to give you antihistamine, anti-fever, and/or steroid medications before your infusions to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur after receiving these medications.
  • If severe IARs occur, your doctor should discontinue XENPOZYME immediately and initiate appropriate medical treatment.
  • If a mild or moderate IAR occurs, your doctor may adjust or temporarily withhold your infusion rate or dose of XENPOZYME.

The most frequent IARs in:
  • adult patients were headache, rash, vomiting, and hives;
  • pediatric patients were hives, swelling, headache, nausea, fever, and vomiting.

An acute phase reaction (APR), an acute inflammatory response accompanied by elevations in inflammatory protein concentrations from blood tests, was observed.
  • Most of the APRs occurred at 48 hours post infusion during the dose escalation period.
  • The most common symptoms of APRs were fever, vomiting, and diarrhea.
  • Your doctor can manage APRs like other IARs you may experience.

Elevated Transaminases Levels
XENPOZYME may be associated with elevated liver enzymes, known as transaminases, within 24 to 48 hours after infusion.
  • Elevated transaminase levels were reported in patients during the XENPOZYME dose escalation phase in clinical trials.

To manage the risk of elevated transaminase levels, your doctor should check your liver enzyme levels with a blood test:
  • within one month before starting XENPOZYME;
  • within 72 hours before any infusion during the dose escalation phase, or before your next scheduled XENPOZYME infusion if you missed a dose.

Based on the levels of transaminases from your blood tests, your doctor may make changes to your dose or infusion schedule.
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
XENPOZYME dosage initiation or escalation, for a female at any time during her pregnancy, is not recommended as it may increase risk of defects in the fetus. The decision to continue or discontinue XENPOZYME maintenance dosing, if you are a pregnant female, should be determined by you and your doctor and should consider your need for XENPOZYME, the potential drug-related risks to the fetus, and the potential risks due to untreated maternal ASMD disease.
If you are a female of reproductive potential, your doctor will verify your pregnancy status before you start treatment with XENPOZYME. You should use effective contraception during XENPOZYME treatment and for 14 days after your last dose if XENPOZYME is discontinued.
ADVERSE REACTIONS
  • Most frequently reported adverse drug reactions in adults (incidence ≥10%) were headache, cough, diarrhea, low blood pressure, and redness in the eye.
  • Most frequently reported adverse drug reactions in pediatric patients (incidence ≥20%) were fever, cough, diarrhea, runny nose, abdominal pain, vomiting, headache, hives, nausea, rash, joint pain, itchy skin, fatigue, and sore throat.

INDICATIONS AND USAGE
XENPOZYME (olipudase alfa-rpcp) is indicated for treatment of non–central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in adult and pediatric patients.
Please see full Prescribing Information, including Boxed WARNING, for complete details.