Xenpozyme

Generic name: olipudase alfa-rpcp
Dosage form: intravenous (infusion) injection
Drug class: Lysosomal enzymes

Medically reviewed by Philip Thornton, DipPharm. Last updated on Aug 23, 2023.

What is Xenpozyme?

Xenpozyme (olipudase alfa-rpcp) is an enzyme replacement therapy used for the treatment of Acid Sphingomyelinase Deficiency (ASMD). ASMD is a rare, progressive, inherited disease that was previously known as Niemann-Pick disease types A, A/B and B.

ASMD is a type of lysosomal storage disease that is caused by the lack of a properly working enzyme known as acid sphingomyelinase (ASM). The production of this enzyme is controlled by a gene called SMPD1. Changes in the SMPD1 gene in people with ASMD mean that they don't produce enough of the ASM enzyme to break down a fatty substance in their cells called sphingomyelin. This leads to the build up of sphingomyelin, which damages multiple organs including the liver, lungs, spleen and heart. ASMD can also affect the digestive system and blood.

Xenpozyme works by supplying olipudase alfa-rpcp, which works the same way the natural ASM enzyme does.

When Xenpoyme was approved by the US Food and Drug Administration (FDA) in August 2022, it was the first and only treatment to have been approved for non-central nervous system manifestations of ASMD in adults and children.

What is Xenpozyme used for?

Xenpozyme is a prescription medication used for the treatment of non–central nervous system manifestations of ASMD in adult and pediatric patients.

Important information

Xenpozyme can cause serious side effects including:

1. 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 this medication.
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.

2. 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 this medication.

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.

3. 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 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 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.

4. 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 maintenance dosing, if you are a pregnant female, should be determined by you and your doctor and should consider your need for this medication, 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 treatment and for 14 days after your last dose if this medication is discontinued.

Who should not receive Xenpozyme?

Do not receive Xenpozyme if you have had life-threatening allergic reactions to olipudase alfa-rpcp or any of the other ingredients in this medication.

What should I tell my doctor before receiving Xenpozyme?

Before starting Xenpozyme, tell your healthcare provider about all of your medical conditions.

How should I receive Xenpozyme?

Xenpozyme will be given by a healthcare professional in an infusion center or your home if your infusions are going well.
It is given by intravenous (IV) infusion (drip) into your vein every two weeks.
Each infusion usually last about three to four hours.
Xenpozyme comes as a powder that is mixed with sterile water before it is administered.
You may be given other medications first to help prevent side effects.

What happens if I miss a dose?

It is important to receive Xenpozyme every two weeks. A dose is considered missed if it's not given within three days of the scheduled date. If you miss a treatment, call your healthcare professional straight away to re-schedule. Adjustments to the dose you receive may need to be made depending on how many doses you have missed.

What happens if I overdose?

An overdose of Xenpozyme is unlikely because it is given by a healthcare professional. However, tell your healthcare professional straight away if you think you have received too much of this medication.

What should I avoid while receiving Xenpozyme?

Xenpozyme may make you feel faint if it causes you to experience low blood pressure. This may affect your ability to drive or use machines. Avoid driving and using machines until you know how this medication affects you.

Dosing information

The recommended adult and pediatric dosages of Xenpozyme for the dose escalation and maintenance phases are based on body weight as follows for patients with a body mass index (BMI):

≤ 30 - the dosage is based on actual body weight (kg)
> 30 - the dosage is based on adjusted body weight (kg). Calculate an adjusted body weight (kg) based on height in meters. Adjusted body weight (kg) = (actual height in m)² x 30

Adults

The recommended adult starting dose of Xenpozyme is 0.1 mg/kg administer as an IV infusion.

The recommended Xenopzyme dose escalation regimen is listed in the table below.

Adult Patients 18 years and older
Week 0/Day 1	First dose	0.1 mg/kg
Week 2	Second dose	0.3 mg/kg
Week 4	Third dose	0.3 mg/kg
Week 6	Fourth dose	0.6 mg/kg
Week 8	Fifth dose	0.6 mg/kg
Week 10	Sixth dose	1 mg/kg
Week 12	Seventh dose	2 mg/kg
Week 14	Eighth dose	3 mg/kg

The recommended adult maintenance dose of Xenopzyme is 3 mg/kg via IV infusion every 2 weeks.

Pediatric patients

The recommended pediatric starting dose of Xenopozyme is 0.03 mg/kg administered as an IV infusion.

The recommended Xenopzyme dose escalation regimen is listed in the table below.

Pediatric Patients 0 to 17 years
Week 0/Day 1	First dose	0.03 mg/kg
Week 2	Second dose	0.1 mg/kg
Week 4	Third dose	0.3 mg/kg
Week 6	Fourth dose	0.3 mg/kg
Week 8	Fifth dose	0.6 mg/kg
Week 10	Sixth dose	0.6 mg/kg
Week 12	Seventh dose	1 mg/kg
Week 14	Eighth dose	2 mg/kg
Week 16	Ninth dose	3 mg/kg

The recommended pediatric maintenance dose of Xenopzyme is 3 mg/kg via IV infusion every 2 weeks.

What are the side effects of Xenpozyme?

Serious side effects of Xenpozyme include:

See 'Important information' above

The most common side effects of Xenpozyme in adult patients (incidence ≥10%) are:

Headache
Cough
Diarrhea
Hypotension
Ocular hyperemia

The most common side effects of Xenpozyme in pediatric patients (incidence ≥20%) are:

Pyrexia
Cough
Diarrhea
Rhinitis
Abdominal pain
Vomiting
Headache
Urticaria
Nausea
Rash
Arthralgia
Pruritus
Fatigue
Pharyngitis

These are not all of the possible side effects of this medication. Call your healthcare professional for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Interactions

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Pregnancy and breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant. The initiation or escalation of Xenpozyme dosing is not recommended during pregnancy as it may increase risk of defects in the fetus. The decision to continue or discontinue maintenance dosing, if you are a pregnant female, should be determined by you and your doctor and should consider your need for this medication, 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 this medication. You should use effective contraception during Xenpozyme treatment and for 14 days after your last dose if treatment is discontinued.

Tell your doctor if your are breastfeeding or plan to breastfeed. It is likely that Xenpozyme is found in breastmilk. Talk to your doctor about the best way to feed your baby while receiving this medication.

Storage

Store Xenpozyme in a refrigerator at 2°C to 8°C (36°F to 46°F).
Do not freeze.
Store reconstituted vials that are not used immediately in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 12 hours.
Store diluted solution that is not being administered immediately in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature at 20°C to 25°C (68°F to 77°F) for up to 12 hours (including infusion time).

Keep out of sight and reach of children.

What are the ingredients in Xenpozyme?

Active ingredient: olipudase alfa-rpcp

Inactive ingredients: dibasic sodium phosphate, methionine, monobasic sodium phosphate, and sucrose

Xenpozyme is manufactured by Genzyme Corporation, a subsidiary of Sanofi.

Popular FAQ

How effective is Xenpozyme?

Treatment with Xenpozyme is effective in adults and children and can significantly improve lung function, reduce liver and spleen size, and increase platelet counts. It can also improve lipid profiles and growth in children.

Clinical trial results show that Xenpozyme starts working by week 26 of treatment. After 26 weeks of treatment with Xenpozyme, significant improvements in a range of measures were noted during clinical studies and levels of sphingomyelin were decreased. Continue reading

How does Xenpozyme work?

Xenpozyme (olipudase alfa-rpcp) is an enzyme replacement therapy that works by providing a functional man-made enzyme to replace acid sphingomyelinase (ASM), an enzyme lacking in people with ASM deficiency (ASMD).

Xenpozyme does not cure ASMD, but simply provides another source of the enzyme for people unable to make enough functional ASM enzyme of their own.

Xenpozyme needs to be taken on an ongoing basis and is administered via intravenous (IV) infusion every two weeks. Continue reading