EXPERIENCE WITH KUVAN
®
In July 2005, Katherine consented to participate in the Kuvan
®
clinical trial
programme. At this stage she was taking 10 exchanges and four PKU
supplements per day.
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Screening study This trial tested for responsiveness. Katherine took Kuvan
®
KUVAN
®
CASE STUDY
10 mg/kg for eight days without altering her normal dietary intake. Her Phe levels
fell by 76% (from 879 µmol/L to 213 µmol/L), which meant that she qualified as a
‘responder’ and was able to continue into the placebo-controlled trial.
Adults and children with hyperphenylalaninaemia (HPA) due to BH
Extension study This trial experimented with different doses of Kuvan
®
.
4
deficiency, and
adults and children over the age of four years with HPA caused by phenylketonuria
Katherine took 5 mg/kg of Kuvan
®
for two weeks, at which point her blood Phe
(PKU), can now be offered the oral treatment sapropterin dihydrochloride (Kuvan
®
). level was 572 µmol/L. After her dose was increased to 20 mg/kg for two weeks
Responsiveness to Kuvan
®
must be established before long-term treatment can be
her blood Phe level was 316 µmol/L.
commenced.
1
A four-week trial with Kuvan
®
is recommended, starting with 10 mg/kg/day.
Long-term study In this long-term study, Katherine took 15 mg/kg of Kuvan
®
per
This can be increased to 20 mg/kg if a satisfactory response ( *30% decrease in blood
phenylalanine; Phe) is not achieved after one week.
1
day and had an average blood Phe level of 661 µmol/L (range: 492–755).
Trials have shown that patients with mild HPA are most likely to respond to Kuvan
®
, but
responsiveness has been observed across the HPA/PKU population.
2
In responders, the
KATHERINE TODAY
number of patients achieving a Phe target of <360 µmol/L was significantly increased in
those taking Kuvan
®
compared to placebo.
3
In a separate trial, children compliant with a
Katherine has continued on a dose of 15 mg/kg (this equates to 11 tablets
Phe-restricted diet who responded to Kuvan
®
were able to increase their daily Phe dissolved in water) and has increased her daily exchanges from 10 to 20 since
supplement by 21 mg/kg/day compared to baseline.
4
completing the trial. She is still quite restrictive with her diet, but has been able to
This is the first of three case studies that describes a patient who has been treated with incorporate a range of new foods including meats and cheese.
Kuvan
®
. Her name has been changed to protect her identity. She was treated by the inherited
metabolic disease team at the Charles Dent Metabolic Unit, National Hospital for Neurology
Katherine now reports fewer migraines and has experienced unexpected
and Neurosurgery, London.
improvement in her teeth, eyes and skin condition. She feels more energetic and
finds it easier to combine caring for her husband with work and volunteering.
CASE HISTORY CONCLUSION
Katherine is a 51-year-old healthcare assistant. She cares for her sick husband This patient was relatively well controlled, but since starting Kuvan
®
she has
and volunteers for a learning disability group. She suffers from mild asthma and been able to relax her diet from 10 to 20 exchanges and maintain a lower blood
occasional migraines but is otherwise fit and well. Phe level. She also reports physical and psychological improvements.
Katherine’s PKU was not diagnosed until she was nine years of age, as she was
born before the introduction of post-natal screening. Katherine struggled with
school, which prompted a series of investigations and the eventual diagnosis of
IN BRIEF
PKU. She left school aged 16 with low-grade passes in English and cookery and
attended college. At age 21 she took a job as a healthcare assistant.
U � x � � � i > � � � � ` � � � � > � � ` � > } � � � i ` � � � � � � * 1 � > � � > } i � � � � i > � �
U � i } > � � � � > �
®
� � � � > � � � � � � � � x � > � ` � � > � � V � � � � � � i ` � � � i > � � i � � � � � � V i � � � i �
DIET
U � � i � � � > � � � i � > � i ` � v � � � � � � � � � � � � � i � V � > � } i � � � i � � ` > �
Following diagnosis, Katherine maintained a strict low-protein diet until the age
U � , i � � � � � � � � V � i > � i ` � i � i � } � � > � ` � V � � V i � � � > � � � � � > � ` � v i � i � � � � } � > � � i �
of 16, but found it difficult to stick to her diet and supplements while at college. U � � � � � � i ` � > L � � � � � � � � manage Phe levels
When she was referred to the adult metabolic clinic at the age of 21, her Phe
levels were 1848 µmol/L, which is far in excess of the target range (120–480
µmol/L, although levels up to 700 µmol/L can be accepted
5
). With the help of the
clinic she stabilised her diet and has managed well over the years with 10 daily
exchanges, low-protein foods, and supplements.
REFERENCES
In 2004–2005, Katherine began to find it increasingly difficult to control her blood
1. Kuvan (sapropterin dihydrochloride) Summary of Product
Characteristics. Merck Serono, December 2008. 2. Burton
Phe levels which ranged from 570–1030 µmol/L (mean: 797 µmol/L). She was BK et al. J Inherit Metab Dis 2007; 30: 700–707. 3. Levy
feeling lethargic, depressed and was suffering with poor concentration and an
HL et al. Lancet 2007; 370: 504–510. 4. Trefz FK et al. J
increased number of migraines. She considered coming off the diet in order to
Paediatr 2009; 154: 700–707. 5. NSPKU. Management of
PKU. February 2004. Available at http://www.nspku.org/ Date of Preparation: October 2009
improve her quality of life. Documents/Management%20of%20PKU.pdf Job Number: KUV09-0103
Prescribing Information
overall protein intake while taking Kuvan is required to ensure adequate control of blood phenylalanine
and tyrosine levels and nutritional balance. Consultation with a physician is recommended during
Please refer to the Summary of Product Characteristics for further information
illness as blood phenylalanine levels may increase. There are limited data regarding the long-term use
Kuvan
®
T100 mg soluble tablets. Sapropterin dihydrochloride. Presentation Off-white to light
of Kuvan. Caution is advised when sapropterin is used in patients with predisposition to convulsions.
yellow soluble tablet with “177” imprinted on one face. Each tablet contains 100 mg of sapropterin
Sapropterin should be used with caution in patients who are receiving concomitant levodopa, inhibitors
dihydrochloride (equivalent to 77 mg of sapropterin). Indications Treatment of hyperphenylalaninaemia
of dihydrofolate reductase or agents causing vasodilation by affecting nitric oxide metabolism or action.
(HPA) in adult and paediatric patients of 4 years of age and over with phenylketonuria (PKU) who
Pregnancy and lactation Kuvan should be considered only if strict dietary management does not
have been shown to be responsive to such treatment. Treatment of hyperphenylalaninaemia (HPA) in
adequately reduce blood phenylalanine levels. Caution must be exercised when prescribing to pregnant
adult and paediatric patients with tetrahydrobiopterin (BH4) deficiency who have been shown to be
responsive to such treatment. Dosage and administration Treatment must be initiated and supervised
women. Kuvan should not be used during breast-feeding. Side effects Side effects include: Headache,
by a physician experienced in PKU and BH4 deficiency. The tablets should be administered as a single
Rhinorrhoea, Pharyngolaryngeal pain, Nasal congestion, Cough, Diarrhoea
daily dose with a meal, and at the same time each day, preferably in the morning. Patients should be
Vomiting, Abdominal pain, Hypophenylalaninemia. Rebound, as defined by an increase in blood
advised not to swallow the desiccant capsule found in the bottle. PKU The starting dose is 10 mg/
phenylalanine levels above pre-treatment levels, may occur upon cessation of treatment. Prescribers
kg body weight once daily. The dose is adjusted, usually between 5 and 20 mg/kg/day, to achieve and
should consult the Summary of Product Characteristics for further information on side effects.
maintain adequate blood phenylalanine levels as defined by the physician. BH4 deficiency The starting
Legal category POM Basic NHS price Kuvan 100mg tablets (30) £597.22 Kuvan 100mg tablets
dose is 2 to 5 mg/kg body weight once daily. Doses may be adjusted up to 20 mg/kg/day. It may be
(120) £2,388.88 Marketing Authorisation Holder and Numbers: Merck KGaA, Frankfurter Str. 250
necessary to divide the total daily dose into 2 or 3 administrations, distributed over the day, to optimise
64293 Darmstadt, Germany EU/1/08/481/001 (30 tablets) EU/1/08/481/002 (120 tablets) For further
the therapeutic effect. Adults The prescribed number of tablets should be placed in a glass or cup with
information, including price queries, contact: UK: Merck Serono Ltd, Bedfont Cross, Stanwell Road,
120 to 240 ml of water and stirred until dissolved. Paediatric patients The prescribed number of tablets
Feltham, Middlesex, TW14 8NX. Tel: 020 8818 7373 Republic of Ireland: Merck Serono, 3013 Lake
should be placed in a glass or cup with up to 120 ml of water and stirred until dissolved. Kuvan has not
Drive, Citywest Business Campus, Dublin 24. Tel: 01 4661910 Date of Preparation: August 2009 Job
been specifically studied in paediatric patients under 4 years of age. Safety and efficacy of Kuvan in
Number: KUV09-0093
patients above 65 years of age or with renal or hepatic insufficiency have not been established. Caution
must be exercised when prescribing to such patients. Contraindications Hypersensitivity to the active Adverse events should be reported. Reporting forms and information can be found at www.
substance or to any of the excipients. Precautions Patients must continue a restricted phenylalanine diet yellowcard.gov.uk. In the Republic of Ireland information can be found at www.imb.ie.
and undergo regular clinical assessment (such as monitoring of blood phenylalanine and tyrosine levels,
Adverse events should also be reported to Merck Serono Limited - Tel: +44(0)20 8818 7373
nutrient intake, and psycho-motor development). Active management of dietary phenylalanine and
medinfo.uk@merckserono.net.
V1 Kuvan_Advert.indd 1 15/10/2009 16:47
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