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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J0000-74

Original Effective Date: 07/15/08

Reviewed: 12/09/13

Revised: 11/01/15

Subject: Sapropterin (Kuvan®) Tablets

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines
           
Other References Update  
           

DESCRIPTION:

Phenylketonuria (PKU) is a rare autosomal recessive inborn error of phenylalanine (Phe) metabolism and a form of hyperphenylalanine (HPA) characterized by elevated blood Phe levels as a result of reduced phenylalanine hydroxylase (PAH) enzyme activity caused by a mutation in the PAH gene. Sapropterin dihydrochloride (Kuvan) is a cofactor of PAH that can increase endogenous PAH activity and subsequently lower blood Phe levels and increase dietary Phe tolerance in a subset of the PKU population identified as responders. All subtypes of PKU based on clinical severity have shown response to sapropterin therapy; however, large and small population studies have demonstrated that response rates correlate with disease severity, with milder forms of PKU having a higher response frequency. Efforts are underway to identify genotype-phenotype relationship to sapropterin response and the only current method is a trial period on sapropterin therapy with evaluation of pre- and post-sapropterin blood Phe levels or Phe tolerance.

In 2000, the National Institute of Health (NIH) convened an expert panel to develop and publish the first national Consensus Statement in the screening and management of NKU. The 2000 NIH Consensus Statement on PKU includes recommendations such as target blood Phe ranges of 2-6 mg/dL for infants through 12 years of age, 2-15 mg/dL after 12 years of age, and 6 mg/dL three months pre-conception and maintained at 2-6 mg/dL throughout pregnancy. The positive effects of maintaining control of Phe levels lifelong through a restricted-Phe diet are recommended, but not reinforced with outcome data. Questions regarding the potential for subtle suboptimal outcomes of early diet-treated PKU also remained controversial at the time of the 2000 NIH Consensus Statement. In 2010, Enns et al. published a review that assessed PKU patient outcomes since the 2000 NIH Consensus Statement publication. The authors concluded that while many of the recommendations within the 2000 NIH Consensus Statement on PKU may still be valid, recent literature coupled with treatment advances such as the availability of sapropterin provides support for a new NIH Consensus Development Conference to revisit PKU management strategies to optimize patient outcomes. In February 2012, the PKU Scientific Review Conference convened to review the 2000 guidelines in light of new advances in PKU treatment. The recommendations of this panel have not been published.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

I. A preliminary trial of sapropterin (Kuvan) for the treatment of phenylketonuria meets the definition of medical necessity when ALL of the following criteria are met:

Approval duration: 60 days

II. Continuation of sapropterin therapy (i.e., following a preliminary trial) meets the definition of medical necessity when ALL of the following criteria are met:

Approval duration: 10 months

III. Long-term sapropterin therapy (i.e., beyond initial 12 months) meets the definition of medical necessity when ALL of the following criteria are met:

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: sapropterin is indicated to reduce blood Phe levels in individuals with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin-(BH4) responsive phenylketonuria (PKU). Sapropterin should be administered in conjunction with a Phe-restricted diet. Sapropterin should be administered orally with food to increase absorption, preferably at the same time each day. The tablets should be dissolved in 4 to 8 ounces (120 to 240 mL) of water or apple juice and taken within 15 minutes of dissolution. Stirring or crushing tablets may allow tablets to dissolve faster; tablets may not dissolve completely.

Dosage Adjustments

Missed Dose: A missed dose should be taken as soon as possible, but 2 doses should not be taken on the same day.

Dosage Availability: sapropterin is available as an unscored, uncoated, immediate-release 100 mg tablet.

PRECAUTIONS:

BILLING/CODING INFORMATION:

The following codes may be used to describe:

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

E70.0

Classical phenylketonuria

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

Phenylketonuria (PKU): the most severe manifestation of hyperphenylalaninemia, inherited as an autosomal recessive trait and due to phenylalanine 4-monooxygenase deficiency, with accumulation and excretion of phenylalanine, phenylpyruvic acid and related compounds. It is characterized by severe mental retardation, tumors, seizures, hypopigmentation of hair and skin, exzema and mousy odor, all preventable by early restriction of dietary phenylalanine.

Phenylalanine (Phe): an aromatic essential amino acid, α-amino-β-phenylpropionic acid; most of that ingested is hydroxylated to form tyrosine, which is used for protein synthesis, but small amounts are transaminated to phenylpyruvic acid or decarboxylated.

RELATED GUIDELINES:

None applicable.

OTHER:

None applicable.

REFERENCES:

  1. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet 2010;376:1417-27.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2012. URL: www.clinicalpharmacology-ip.com. Accessed 11/18/2013.
  3. Cunningham A, Bausell H, Brown M et al. Recommendations for the use of sapropterin in phenylketonuria. Mol Genet Metab 2012;106:269-76.
  4. Enns GM, Koch R, Brumm V et al. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab 2010;101:99-109.
  5. Ingenix ICD-9-CM for Physicians-Volumes 1 & 2, Expert 2013
  6. Kuvan (sapropterin dihydrochloride) [package insert]. BioMarin Pharmaceutical Inc. Novato (CA): December 2007.
  7. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 11/18/2013.
  8. Sapropterin In: McEvoy GK, editor. AHFS drug information 2013 [monograph on the Internet]. Bethesda (MD): American Society of Health-System Pharmtacists; 2013 [cited 2013 November 18]. Available from: http://online.statref.com. Subscription required to view

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 12/09/13.

GUIDELINE UPDATE INFORMATION:

07/15/08

New Medical Coverage Guideline.

07/15/09

Review and revision; consisting of updating precautions section and updating references.

01/15/11

Review and revision; consisting of updating references, and adding ICD-10 codes.

01/15/12

Review and revision to guideline; consisting of updating coding, precautions and references.

01/15/13

Review and revision to guideline; consisting of revising and reformatting position statement; revising decision, dosage/administration/precautions sections; updating references.

01/15/14

Review and revision to guideline; consisting of reformatting position statement, updating references, program exceptions and changing status to no longer reviewed.

06/15/15

Revision to guideline; consisting of position statement

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: August 23, 2017: 01:20 PM