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.

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.

• 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.

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.

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.

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

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.

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.

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.

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.

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.