Oral powder in sachets for the treatment of hyperphenylalaninemia in patients with phenylketonuria (PKU)

About the medicinal product

Sephience contains the active substance sepiapterin.

Sephience is used to treat hyperphenylalaninemia^[1] in patients of all ages with phenylketonuria (PKU) who are responsive to this treatment.

PKU is a hereditary metabolic disorder in which those affected cannot properly break down phenylalanine^[2], which can lead to dangerous accumulations in the blood and brain. Sepiapterin helps to reduce these surpluses, thereby reducing dangerous levels of phenylalanine in the blood.

^[1] _{Hyperphenylalaninemia is a condition in which phenylalanine levels in the blood are elevated.}

^[2] _{Phenylalanine: An essential amino acid ingested in food which acts as a building block for important substances in the body.}

Mode of action

Sephience contains the active substance sepiapterin, which is similar to the natural substance in the body that helps to break down the amino acid phenylalanine. In phenylketonuria (PKU), this breakdown process does not work properly and too much phenylalanine can accumulate in the blood and brain, which can be dangerous. Sepiapterin is converted in the body into a substance called tetrahydrobiopterin (BH4). This helps to reduce the quantity of phenylalanine in the blood by supporting the activity of a specific enzyme^[3] which is responsible for breaking down phenylalanine.

^[3] _{Enzymes: special proteins that speed up chemical reactions in the body.}

Administration

Sephience is a prescription-only medicine.

Sephience is available as an oral powder in sachets in 250 mg and 1000 mg doses.

The recommended dosage of Sephience is based on the age and body weight of the patient. In patients aged 2 years or older, the recommended dosage is 60 mg/kg/day. Younger children receive a lower dosage adjusted to their age. The powder is taken once daily and can be dissolved in liquids such as water or apple juice.

Efficacy

The efficacy of Sephience was investigated in a 2-part study (PTC923-MD-003-PKU).

To determine the efficacy of Sephience in the treatment of phenylketonuria (PKU), the study was divided into 2 parts in which the patients were assessed. In part 1, the participants received Sephience for 14 days to ascertain which of them were responsive to it. After at least a 14-day break without taking medication, the participants who were responsive in part 1 were treated over a 6-week period in part 2. They were allocated at random to receive either gradually increasing doses of Sephience or a placebo (dummy drug). The results showed a signification reduction of phenylalanine levels in the blood, which confirmed the efficacy of Sephience in patients who are responsive to the medicinal product.

Precautions, undesirable effects & risks

Sephience may not be used in those who are hypersensitive to the active substance or any of the excipients.

The most common undesirable effects (affecting more than 1 in 10 patients) are diarrhoea, abdominal pain, upper respiratory track infection (cold), and headache.

Regular medical check-ups are required during treatment with Sephience in order to measure phenylalanine levels in the blood.

All precautions, risks, and other possible undesirable effects are listed in the Information for patients (package leaflet) and the Information for healthcare professionals.

Why the medicinal product has been authorised

A lifelong low-phenylalanine diet is required in the treatment of phenylketonuria (PKU); adherence to this is particularly difficult for adolescents and adults. Sepiapterin represents a new treatment option which can be used in addition to dietary therapy to keep phenylalanine levels in the blood lower over the long term and improve quality of life.

The relevant pivotal studies showed that a significant reduction of phenylalanine levels in the blood could be achieved in patients who received and responded to Sephience.

Taking all the risks and precautions into account, and based on the available data, the benefits of Sephience outweigh the risks. Swissmedic has therefore authorised the medicinal product Sephience, containing the active substance sepiapterin, for use in Switzerland.

Further information on the medicinal product

Information for healthcare professionals:

Information for patients (package leaflet):

Healthcare professionals can answer any further questions.

^{The date of revision of this text corresponds to that of the SwissPAR. New information concerning the authorised medicinal product in question will not be incorporated into the Summary report on authorisation.}

^{Swissmedic monitors medicinal products authorised in Switzerland. Swissmedic initiates the necessary action in the event of newly discovered adverse drug reactions or other safety-relevant signals. New findings that could impair the quality, efficacy, or safety of this medicinal product are recorded and published by Swissmedic. If necessary, the medicinal product information is adapted.}