Kuvan

sapropterin

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This is a summary of the European public assessment report (EPAR) for Kuvan. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Kuvan.

What is Kuvan?

Kuvan is a medicine that contains the active substance sapropterin dihydrochloride. It is available as soluble tablets (100 mg).

What is Kuvan used for?

Kuvan is used to treat high blood levels of phenylalanine in adults and children of all ages with the genetic disorders phenylketonuria (PKU) or tetrahydrobiopterin (BH4) deficiency.

Patients with these disorders cannot process the amino acid phenylalanine from dietary protein, and as a result the amino acid builds up in the blood to abnormally high levels, causing problems in the nervous system.

Because the number of patients with conditions leading to high phenylalanine levels is low, they are considered ‘rare’, and Kuvan was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 8 June 2004.

The medicine can only be obtained with a prescription.

How is Kuvan used?

Treatment with Kuvan must be started and supervised by a doctor who has experience in treating PKU and BH4 deficiency. It is important that patients continue with a diet low in phenylalanine and protein when taking Kuvan, and intake of phenylalanine and protein must be monitored and adjusted to make sure that blood phenylalanine levels and nutritional balance are controlled. Kuvan is intended for long-term use.

The dose of Kuvan depends on the patient’s weight. Kuvan is taken with a meal at the same time every day, preferably in the morning. The tablets are dissolved in water before the patient drinks the solution. For some patients with BH4 deficiency, the dose may need to be divided into two or three doses over the course of the day to get the best effect.

A satisfactory response is defined as a reduction in blood phenylalanine levels of at least 30% or to a level determined by the doctor. If this has been achieved after one month, the patient is classified as a ‘responder’ and can continue taking Kuvan.

How does Kuvan work?

The high levels of phenylalanine in the blood are due to a problem with the conversion of phenylalanine into tyrosine by the enzyme ‘phenylalanine hydroxylase’. Patients with PKU have defective versions of the enzyme, and patients with BH4 deficiency have low levels of BH4, a ‘cofactor’ that this enzyme needs to work properly.

The active substance in Kuvan, sapropterin dihydrochloride, is a synthetic copy of BH4. In PKU, it works by enhancing the activity of the defective enzyme, while in BH4 deficiency it replaces the missing cofactor. These actions help restore the ability of the enzyme to convert phenylalanine into tyrosine, thereby reducing phenylalanine levels in the blood.

How has Kuvan been studied?

In PKU treatment, a main study compared the reductions in blood phenylalanine in 88 patients treated with either Kuvan or placebo (a dummy treatment). Two other studies in 101 patients looked at how effective Kuvan was at allowing the patients to consume foods containing phenylalanine while keeping blood phenylalanine at target levels (i.e. phenylalanine tolerance)

For the treatment of BH4 deficiency, which is a very rare condition, the company presented results of three studies from the published literature in which some patients were treated with sapropterin for an average of 15.5 months.

Studies with Kuvan involved adults and children of all ages.

What benefit has Kuvan shown during the studies?

Kuvan was more effective than placebo at reducing blood phenylalanine levels in patients with PKU, achieving a reduction of 236 micromoles per litre after 6 weeks compared with an increase of 3 micromoles per litre seen with placebo.

In addition Kuvan allowed patients with PKU who were not on a diet restriction to increase their daily phenylalanine intake by 17.5 mg per kg body weight after 10 weeks compared with 3.3 mg/kg with placebo. When Kuvan plus diet restriction was compared with diet restriction alone, the average daily phenylalanine intake that was tolerated after 26 weeks was 81 mg/kg in the Kuvan group and 50 mg/kg in the group on diet restriction alone.

In the studies of patients with BH4 deficiency, patients showed an improvement in blood phenylalanine levels and other markers of the disease when they were taking sapropterin dihydrochloride.

What is the risk associated with Kuvan?

The most common side effects with Kuvan (seen in more than 1 patient in 10) are headache and rhinorrhoea (runny nose). For the full list of all side effects reported with Kuvan, see the package leaflet.

Why has Kuvan been approved?

The CHMP decided that Kuvan’s benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Kuvan?

A risk management plan has been developed to ensure that Kuvan is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Kuvan, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Kuvan

The European Commission granted a marketing authorisation valid throughout the European Union for Kuvan on 2 December 2008.

For more information about treatment with Kuvan, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

Name Language First published Last updated
Kuvan : EPAR - Summary for the public BG = bălgarski 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public ES = español 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public CS = čeština 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public DA = dansk 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public DE = Deutsch 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public ET = eesti keel 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public EL = elliniká 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public EN = English 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public FR = français 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public IT = italiano 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public LV = latviešu valoda 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public LT = lietuvių kalba 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public HU = magyar 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public MT = Malti 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public NL = Nederlands 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public PL = polski 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public PT = português 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public RO = română 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public SK = slovenčina 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public SL = slovenščina 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public FI = suomi 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public SV = svenska 16/01/2009 03/08/2015
Kuvan : EPAR - Summary for the public HR = Hrvatski 16/01/2009 03/08/2015

This EPAR was last updated on 03/08/2015 .

Authorisation details

Product details

Product details for Kuvan
NameKuvan
Agency product numberEMEA/H/C/000943
Active substance

sapropterin dihydrochloride

International non-proprietary name (INN) or common name

sapropterin

Therapeutic area Phenylketonurias
Anatomical therapeutic chemical (ATC) code A16AX07
Treatment of rare diseases

This medicine has an "orphan designation" which means that it is used to treat life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the European Union, or are medicines which, for economic reasons, would be unlikely to be developed without incentives.

Publication details

Publication details for Kuvan
Marketing-authorisation holder

Merck Serono Europe Limited

Revision9
Date of issue of marketing authorisation valid throughout the European Union02/12/2008

Contact address:

Merck Serono Europe Limited
56 Marsh Wall
London E14 9TP
United Kingdom

Product information

Product information

22/06/2015  Kuvan -EMEA/H/C/000943 -II/0033

Name Language First published Last updated
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015
Kuvan : EPAR - Product Information HR = Hrvatski 27/07/2009 03/08/2015

Contents

  • Annex I - Summary of product characteristics
  • Annex IIA - Manufacturing-authorisation holder responsible for batch release
  • Annex IIB - Conditions of the marketing authorisation
  • Annex IIIA - Labelling
  • Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.


Name Language First published Last updated
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  
Kuvan : EPAR - All Authorised presentations HR = Hrvatski 16/01/2009  

Pharmacotherapeutic group

Other alimentary tract and metabolism products

Therapeutic indication

Kuvan is indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with phenylketonuria (PKU) who have been shown to be responsive to such treatment (see section 4.2).

Kuvan is also indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with tetrahydrobiopterin (BH4) deficiency who have been shown to be responsive to such treatment (see section 4.2).

Assessment History

Changes since initial authorisation of medicine

Initial marketing-authorisation documents

Name Language First published Last updated
Kuvan : EPAR - Public assessment report HR = Hrvatski 10/04/2009  
Committee for medicinal products for human use, summary of positive opinion for Kuvan HR = Hrvatski 25/09/2008