Xenpozyme (olipudase alfa-rpcp)

Dosage of olipudase alfa-rpcp in adults and pediatric patients is based on weight. Use actual body weight in patients with BMI <=30 kg/m2. In patients with BMI >30 kg/m2, use an adjusted body weight calculated by the following formula: adjusted body weight (kg) = (actual height in m)2 x 30.

Treatment with olipudase alfa-rpcp should always be initiated via a dose escalation regimen followed by a maintenance dose. The recommended initial dosage of olipudase alfa-rpcp in pediatric patients is 0.03 mg/kg, and the recommended maintenance dosage in pediatric patients is 3 mg/kg every 2 weeks. To reduce the risk of hypersensitivity and IARs or elevated transaminase levels, follow the recommended dosage titration schedule shown in Table 5.

Table 5. Olipudase Alfa-rpcp Dose Escalation Regimen for Pediatric Patients 0-17 Years of Age

Dose Number Dosage based on Actual or Adjusted Weight First dose (day 1/week 0) 0.03 mg/kg Second dose (week 2) 0.1 mg/kg Third dose (week 4) 0.3 mg/kg Fourth dose (week 6) 0.3 mg/kg Fifth dose (week 8) 0.6 mg/kg Sixth dose (week 10) 0.6 mg/kg Seventh dose (week 12) 1 mg/kg Eighth dose (week 14) 2 mg/kg Ninth dose (week 16) 3 mg/kg (recommended maintenance dose)

The recommended initial dosage of olipudase alfa-rpcp in adults is 0.1 mg/kg, and the recommended maintenance dosage in adults is 3 mg/kg every 2 weeks. To reduce the risk of hypersensitivity and IARs or elevated transaminase levels, follow the recommended dosage titration schedule shown in Table 6.

Table 6. Olipudase Alfa-rpcp Dose Escalation Regimen for Adults >=18 Years of Age

Dose Number Dosage based on Actual or Adjusted Weight 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)

Olipudase alfa-rpcp is administered by IV infusion. Olipudase alfa-rpcp therapy should be administered in consultation with healthcare providers knowledgeable in the management of acid sphingomyelinase deficiency. In order to avoid dosing errors, clinicians should follow all instructions for dosage and administration.

Prior to administration, inspect the syringe or infusion bag for foaming; if foaming is present, let the foam dissipate before administering olipudase alfa-rpcp. Administer olipudase alfa-rpcp infusion using an inline, low-protein-binding filter with a pore diameter of 0.2 mcm. The following materials can be used: polyolefin or polyvinylchloride (PVC) with diethylhexylphthalate (DEHP) for infusion bags; polypropylene for syringes; polyurethane or non-DEHP PVC for infusion sets; and polyethersulfone or polytetrafluoroethylene for inline filters. Do not infuse olipudase alfa-rpcp in the same IV line with other drugs. At the end of the infusion, flush the infusion line with 0.9% sodium chloride injection using the same infusion rate as the one used for the last part of the infusion.

Home administration under the supervision of a clinician may be considered for patients receiving a maintenance dose who are tolerating olipudase alfa-rpcp infusions well. The decision to transition patients to home infusion should be made after evaluation and recommendation by a physician. Dosage and infusion rate in the home setting should remain the same as that used in the supervised clinical setting and should not be changed without supervision of an appropriate healthcare provider. In case of a missed dose or delayed infusion, an appropriate healthcare provider should be contacted as subsequent infusions may occur in a supervised clinical setting.

No dosing information is available for this tab.

Formal drug interaction studies with olipudase alfa-rpcp have not been performed to date. As a therapeutic protein, olipudase alfa is unlikely to be involved in cytochrome P-450 (CYP)- or transporter-mediated drug interactions.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

There are no contraindication contraindications for this drug.

• Pregnancy

There are no moderate contraindications for this drug.

Adverse effects reported in >=10% of adults receiving olipudase alfa-rpcp include headache, cough, diarrhea, hypotension, and ocular hyperemia.

Adverse effects reported in >=20% of pediatric patients receiving olipudase alfa-rpcp include pyrexia, cough, diarrhea, rhinitis, abdominal pain, vomiting, headache, urticaria, nausea, rash, arthralgia, pruritus, fatigue, and pharyngitis.

More Frequent

• Hypersensitivity drug reaction
• Hypotension

Less Frequent

• Dyspnea
• Increased alanine transaminase
• Increased aspartate transaminase

Rare or Very Rare

• Anaphylaxis

More Frequent

• Acute abdominal pain
• Arthralgia
• Cough
• Diarrhea
• Fatigue
• Fever
• Headache disorder
• Ocular redness
• Pharyngitis
• Pruritus of skin
• Skin rash
• Vomiting

Less Frequent

• General weakness
• Myalgia
• Tachycardia
• Urticaria

No enhanced messaging available.

Safety and efficacy of olipudase alfa-rpcp for the treatment of non-CNS manifestations of ASMD have been established in pediatric patients, including neonates. Use of olipudase alfa-rpcp for this indication is supported by evidence from an adequate, well-controlled trial in adults (Trial 1) and supportive efficacy, safety, and tolerability data in pediatric patients (Trials 2 and 3). Compared with 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, including a patient 18 months of age receiving olipudase alfa-rpcp and a patient 16 months of age with ASMD type A receiving a version of olipudase alfa manufactured from a different process, developed anaphylaxis.

Based on findings from animal reproduction studies, olipudase alfa-rpcp may cause embryofetal harm when administered to a pregnant female. There are no available data on use of olipudase alfa-rpcp in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In an embryofetal 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.

Initiation or dosage escalation of olipudase alfa-rpcp is not recommended at any time during pregnancy as it may lead to elevated sphingomyelin metabolite levels that may increase the risk of fetal malformations. However, the decision to continue or discontinue maintenance dosing of olipudase alfa-rpcp during pregnancy should consider the female's need for olipudase alfa-rpcp, the potential drug-related risks to the fetus, and potential adverse outcomes from untreated maternal ASMD disease. Advise pregnant females of the potential risk to the fetus.

It is not known whether olipudase alfa-rpcp is distributed into human milk, affects the breast-fed infant, or affects milk production. Olipudase alfa-rpcp is distributed into milk in mice. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for olipudase alfa-rpcp and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Among the adult patients receiving olipudase alfa-rpcp in clinical trials, 3% of patients were >=65 years of age, and none were >=75 years of age. Clinical trials of olipudase alfa-rpcp did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently than younger adults.