Download Kuvan® Covered Medication Sapropterin dihydrochloride (Kuvan

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Kuvan
Covered Medication
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Sapropterin dihydrochloride (Kuvan ) tablets
What it does and how it is used
 Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by increased levels of the
amino acid phenylalanine (Phe) in the blood.
 In the US, newborn screening for PKU is routinely done.
 Phe is widely available through one’s diet. If PKU is left untreated, high levels of Phe result in serious
health effects including mental retardation, behavioral problems, seizures, and developmental delay.
 Patients with PKU often have a musty or mouse-like odor attributed to the high phenylalanine levels.
 Mutations in the phenylalanine hydroxylase (PAH) gene result in PKU. PAH is responsible for converting
Phe into its useful forms for the body.
 Diagnosis can be made in individuals with blood Phe levels over 1200 µM/L. The National Institute of
Health (NIH) recommends target Phe levels for infants and children through 12 years be 2 to 6 mg/dL (120360 µM/L) and 2 to 15 mg/dL (120–900 µM/L) for individuals over age 12. Even lower Phe levels (2 to 10
mg/dL) are encouraged during the teen years while the brain is still developing.
 Current treatment for PKU is a special diet consisting of fruits, vegetables, and other foods low in Phe.
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 Kuvan is the first pharmaceutical indicated to reduce blood Phe levels in patients with
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hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive to PKU. Kuvan is a synthetic
form of BH4, the cofactor for the enzyme phenylalanine hydroxylase (PAH).
 In patients with PKU, PAH activity is absent or deficient. Treatment with BH4 can activate residual PAH
enzyme, improve the normal oxidative metabolism of Phe, and decrease Phe levels in some patients.
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 Kuvan clinical trials showed a reduction in blood Phe levels in some patients when used in conjunction
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with a Phe-restricted diet. Long-term assessment of neurological function in patients receiving Kuvan for
PKU was not assessed.
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 Only 20% to 56% of PKU patients responded to Kuvan therapy. It cannot be predicted who will respond
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and a drug trial is necessary. Therefore, the initiation of Kuvan treatment does not eliminate the need to
monitor blood Phe levels. Also, prolonged levels of low Phe could lead to negative side effects.
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 Some adverse effects observed with Kuvan include: gastritis, spinal cord injury, streptococcal infection,
testicular carcinoma, urinary tract infection, headache, diarrhea, abdominal pain, upper respiratory tract
infection, pharyngolaryngeal pain, nausea, and vomiting.
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 Kuvan is available as a 100mg tablet (contains 100mg sapropterin dihydrochloride which is equivalent to
76.8 mg of sapropterin base) that must be dissolved in liquid for oral administration.
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 Maintenance doses of Kuvan may range from 5 to 20 mg/kg/day and the recommended starting dose is
10 mg/kg/day taken once daily. Response to therapy is determined by change in blood Phe following
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treatment with Kuvan at 10 mg/kg/day for a period of up to 1 month. Blood Phe levels should be checked
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after 1 week of Kuvan treatment and periodically for up to a month. If blood Phe does not decrease from
baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day. Patients whose blood Phe does
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not decrease after 1 month of treatment at 20 mg/kg/day are non-responders, and treatment with Kuvan
should be discontinued in these patients.
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 Kuvan tablets should be administered with food to increase absorption, at the same time each day.
AWP/tablet
$36.25
What it costs
(for 70kg adult at max dose 20 mg/kg/day)
AWP/day
AWP/month
$507.50
$15,225
AWP/year
$182,700
Rationale for prior authorization
To reduce exposure to costs associated with providing coverage in situations in which the drug is ineffective,
such as when the medication will not be taken in conjunction with a Phenylalanine-restricted diet or when a
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patient does not respond to Kuvan .
Benefit design
Coverage is determined through prior authorization for every claim.
Prior authorization criteria
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Coverage for Kuvan is provided for the treatment of phenylketonuria (PKU) in accord with the following:
Copyright© 2010 Medco Health Solutions, Inc. All rights reserved
Used Under License
Kuvan
August 2010
1. Patient must be on a phenylalanine restricted diet.
Coverage duration: Coverage is initially provided for 3 months. Coverage is renewable for 5 years in situations
in which there has been a 30% or more decrease in baseline blood phenylalanine levels OR if less than a 30%
reduction of phenylalanine levels is realized, but NIH recommended target phenylalanine levels are still
achieved [Patients ≤12 years of age: 2 to 6 mg/dL (120–360 µM/L); Patients >12 years of age: 2 to 15 mg/dL
(120–900 µM/L)].
References
 Burton BK, Grange DK, Milanowski A, et al., The response of patients with phenylketonuria and elevated
serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II,
multicentre, open-label, screening study. J Inherit Metab Dis (2007) 30:700–707.
 Genetics Home Reference. National Library of Medicine. http://ghr.nlm.nih.gov/condition=phenylketonuria.
Accessed on 1/8/2008.
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 Kuvan (sapropterin dihydrochloride). Prescribing information. BioMarin Pharmaceutical, Inc. Novato, CA:
November 2007.
 Levy HL, Milanowski A, Chakrapani A, et al., Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin,
6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III
randomized placebo-controlled study. Lancet 2007; 370: 504–10.
 March of Dimes. http://www.marchofdimes.com/pnhec/4439_1219.asp. Accessed on 1/8/2008.
 National Institute of Child Health & Human Development.
http://www.nichd.nih.gov/health/topics/phenylketonuria.cfm. Accessed on 1/8/2008.
 Phenylketonuria: Screening and Management. NIH Consensus Statement Online 2000 October 16-18;
Accessed 18 August 2008; 17(3): 1-27. Available from URL
http://consensus.nih.gov/2000/2000Phenylketonuria113html.htm
Copyright© 2010 Medco Health Solutions, Inc. All rights reserved
Used Under License
Kuvan
August 2010