Hyperphenylalaninaemia (HPA) in patients with phenylketonuria (PKU)

Active Ingredient: Sepiapterin

Indication for Sepiapterin

Population group: only infants (40 days - 1 year old) , children (1 year - 12 years old) , adolescents (12 years - 18 years old) , adults (18 years old or older)
Therapeutic intent: Curative procedure

Sepiapterin is indicated for the treatment of hyperphenylalaninaemia (HPA) in adult and paediatric patients with phenylketonuria (PKU).

For this indication, competent medicine agencies globally authorize below treatments:

7.5-60 mg/kg/day once daily based on age

For:

Dosage regimens

Regimen A, in case that patient age in months is < 6

Oral, 7.5 milligrams sepiapterin per kilogram of body weight, once daily.

Regimen B, in case that patient age in months is ≥ 6 and patient age in months is < 12

Oral, 15 milligrams sepiapterin per kilogram of body weight, once daily.

Regimen C, in case that patient age in months is ≥ 12 and patient age in years is < 2

Oral, 30 milligrams sepiapterin per kilogram of body weight, once daily.

Regimen D, in case that patient age in years is ≥ 2

Oral, 60 milligrams sepiapterin per kilogram of body weight, once daily.

Detailed description

The recommended dose (mg/kg/day) of sepiapterin to be administered orally once daily is based on age and body weight (see table). The maximum recommended dose is 60 mg/kg/day. The recommended dose of sepiapterin in patients ≥2 years of age is 60 mg/kg/day. However, the dose may be adjusted to a lower dose if the treating physician considers it necessary or appropriate.

Recommended dose based on patient's age and body weight:

AgeRecommended dose (mg/kg) of sepiapterin per day
0 to <6 months7.5 mg/kg/day
6 to <12 months15 mg/kg/day
12 months to <2 years30 mg/kg/day
≥2 years60 mg/kg/day

Missed dose

A missed dose should be taken as soon as possible. The normal dosing schedule should be resumed the following day.

Discontinuation of treatment

In the pivotal Phase 3 clinical study, a threshold of 15% or greater reduction in blood phenylalanine (Phe) levels was utilised for determination of response.

No controlled efficacy and safety data are available in patients who do not experience a reduction of 15% or greater reduction in blood Phe levels after receiving sepiapterin for 14 days.

The determination of responsiveness for a patient with PKU and the discontinuation of the medicinal product is at the discretion of the treating physician.

Elderly

The safety and efficacy of sepiapterin in patients 65 years of age and older have not been established. Caution should be exercised when prescribing in patients 65 years of age and older.

Active ingredient

Sepiapterin

Sepiapterin is a natural precursor of the enzymatic co-factor BH4, a critical co-factor for phenylalanine hydroxylase (PAH). Sepiapterin acts as a dual pharmacological chaperone (sepiapterin and BH4 each with its own binding affinity to variant PAH), including PAH variants commonly found in PKU and known to be insensitive to BH4, to improve the activity of the defective PAH enzyme, achieving a high concentration of BH4 intracellularly.

Read more about Sepiapterin

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