The efficacy of XENPOZYME was studied in adult and pediatric trials1

A multicenter, randomized, double-blinded trial in adult patients

Illustration of Xenpozyme clinical trial design in adult patients with ASMD. The 52 week clinical trial consisted of 31 adult patients with ASMD (type B or A/B) with 13 patients who received a Xenpozyme IV infusion once every two weeks and 18 patients that received a placebo. The extension treatment period was less than or equal to 4 years with 30 patients (placebo patients crossed over to active therapy).

In adult patients, XENPOZYME:

Lung icon with text stating improved lung function
Spleen icon  with text stating reduced spleen volume
Liver icon with text stating reduced liver volume
Platelets icon with text stating raised platelet count

A systemic treatment for a multisystemic disease.

A multicenter, open-label, repeated-dose trial in pediatric patients

Illustration of Xenpozyme clinical trial design in pediatric patients with ASMD. The 52 week clinical trial (with a 64 week safety analysis period) consisted of 8 pediatric patients with ASMD (type B or A/B) who received a Xenpozyme IV infusion once every two weeks. The trial included 7 patients ages 2 through 12 years old and 1 patient under 2 years old.

*Patients received XENPOZYME via a dose escalation regimen over a minimum period of 16 weeks from 0.03 mg/kg to a target dose of 3 mg/kg. All but 1 patient completed the dose escalation up to the maintenance dose of 3 mg/kg within 22 weeks.

In pediatric patients, XENPOZYME:

Lung icon with text stating improved lung function
Spleen icon  with text stating reduced spleen volume
Liver icon with text stating reduced liver volume
Platelets icon with text stating raised platelet count
Icon of small child with text stating improved growth patterns in pediatric patients with growth delay

Help patients with ASMD reclaim their potential with XENPOZYME.

ASMD=acid sphingomyelinase deficiency; DLco=diffusing capacity of the lungs for carbon monoxide; IV=intravenous; MN=multiples of normal.

IMPORTANT SAFETY INFORMATION AND INDICATION 

WARNING: SEVERE HYPERSENSITIVITY REACTIONS

Hypersensitivity Reactions Including Anaphylaxis

Patients treated with XENPOZYME have experienced hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during XENPOZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, XENPOZYME should be discontinued immediately, and appropriate medical treatment should be initiated. In patients with severe hypersensitivity reaction, a desensitization procedure to XENPOZYME may be considered.


WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions Including Anaphylaxis

See Boxed WARNING. Prior to XENPOZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids.

  • If a severe hypersensitivity reaction occurs, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following severe hypersensitivity reactions.
  • If a mild or moderate hypersensitivity reaction occurs, the infusion rate may be slowed or temporarily withheld, and/or the XENPOZYME dose reduced.

Infusion-Associated Reactions

Antihistamines, antipyretics, and/or corticosteroids may be given prior to XENPOZYME administration to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur in patients after receiving pretreatment.

  • If severe IARs occur, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following severe IARs.
  • If a mild or moderate IAR occurs, the infusion rate may be slowed or temporarily withheld, and/or the XENPOZYME dosage may be reduced.

An acute phase reaction (APR), an acute inflammatory response accompanied by elevations in inflammatory serum protein concentrations, was observed. Most of the APRs occurred at 48 hours post infusion during the dose escalation period. APRs can be managed as other IARs.

Elevated Transaminases Levels

XENPOZYME may be associated with elevated transaminases (ALT, AST, or both) within 24 to 48 hours after infusion. 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, or prior to the next scheduled XENPOZYME infusion upon resuming treatment following a missed dose.

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, 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 pregnancy status in females of reproductive potential prior to initiating XENPOZYME treatment. Advise females of reproductive potential to use effective contraception during XENPOZYME treatment and for 14 days after the last dose if XENPOZYME is discontinued.

ADVERSE REACTIONS

  • 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.

INDICATION

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.

Reference: 1. XENPOZYME. Prescribing Information.

IMPORTANT SAFETY INFORMATION AND INDICATION 

WARNING: SEVERE HYPERSENSITIVITY REACTIONS

Hypersensitivity Reactions Including Anaphylaxis

Patients treated with XENPOZYME have experienced hypersensitivity reactions, including anaphylaxis. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during XENPOZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, XENPOZYME should be discontinued immediately, and appropriate medical treatment should be initiated. In patients with severe hypersensitivity reaction, a desensitization procedure to XENPOZYME may be considered.


WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions Including Anaphylaxis

See Boxed WARNING. Prior to XENPOZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids.

  • If a severe hypersensitivity reaction occurs, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following severe hypersensitivity reactions.
  • If a mild or moderate hypersensitivity reaction occurs, the infusion rate may be slowed or temporarily withheld, and/or the XENPOZYME dose reduced.

Infusion-Associated Reactions

Antihistamines, antipyretics, and/or corticosteroids may be given prior to XENPOZYME administration to reduce the risk of infusion-associated reactions (IARs). However, IARs may still occur in patients after receiving pretreatment.

  • If severe IARs occur, discontinue XENPOZYME immediately and initiate appropriate medical treatment. Consider the risks and benefits of re-administering XENPOZYME following severe IARs.
  • If a mild or moderate IAR occurs, the infusion rate may be slowed or temporarily withheld, and/or the XENPOZYME dosage may be reduced.

An acute phase reaction (APR), an acute inflammatory response accompanied by elevations in inflammatory serum protein concentrations, was observed. Most of the APRs occurred at 48 hours post infusion during the dose escalation period. APRs can be managed as other IARs.

Elevated Transaminases Levels

XENPOZYME may be associated with elevated transaminases (ALT, AST, or both) within 24 to 48 hours after infusion. 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, or prior to the next scheduled XENPOZYME infusion upon resuming treatment following a missed dose.

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, 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 pregnancy status in females of reproductive potential prior to initiating XENPOZYME treatment. Advise females of reproductive potential to use effective contraception during XENPOZYME treatment and for 14 days after the last dose if XENPOZYME is discontinued.

ADVERSE REACTIONS

  • 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.

INDICATION

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.

Reference: 1. XENPOZYME. Prescribing Information.