Pharmacy Prior Authorization Criteria

Sapropterin Products

Indications for Prior Authorization

Kuvan (sapropterin dihydrochloride)

• For diagnosis of Phenylketonuria
  Indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). It is to be used in conjunction with a Phe-restricted diet.

Javygtor (sapropterin dihydrochloride)

• For diagnosis of Phenylketonuria
  Indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). It is to be used in conjunction with a Phe-restricted diet.

Criteria

Brand Kuvan, Brand Javygtor

Prior Authorization (Initial Authorization)

Length of Approval: 2 Month(s)

• Diagnosis of phenylketonuria (PKU)
AND
• Used in conjunction with a phenylalanine (Phe)-restricted diet [A]
AND
• Patient will have Phe blood levels measured after 1 week of therapy (new starts to therapy only) and periodically for up to 2 months of therapy to determine response [E]
AND
• Trial and failure or intolerance to generic sapropterin

Brand Kuvan, Brand Javygtor

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)

• Patient has had an objective response to therapy, defined as a 30% or greater reduction in phenylalanine (Phe) blood levels from baseline [B -D]
AND
• Used in conjunction with a phenylalanine (Phe)-restricted diet [A]
AND
• Patient will continue to have blood Phe levels measured periodically during therapy [E]
AND
• Trial and failure or intolerance to generic sapropterin

Generic sapropterin

Prior Authorization (Initial Authorization)

Length of Approval: 2 Month(s)

• Diagnosis of phenylketonuria (PKU)
AND
• Used in conjunction with a phenylalanine (Phe)-restricted diet [A]
AND
• Patient will have Phe blood levels measured after 1 week of therapy (new starts to therapy only) and periodically for up to 2 months of therapy to determine response [E]

Generic sapropterin

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)

• Patient has had an objective response to therapy, defined as a 30% or greater reduction in phenylalanine (Phe) blood levels from baseline [B -D]
AND
• Used in conjunction with a phenylalanine (Phe)-restricted diet [A]
AND
• Patient will continue to have blood Phe levels measured periodically during therapy [E]

P & T Revisions

2024-10-02, 2023-10-02, 2022-11-02, 2022-09-28, 2021-09-27, 2021-04-14, 2021-03-04, 2020-09-30

References

1. Kuvan prescribing information. BioMarin Pharmaceutical Inc. Novato, CA. August 2024.
2. 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 randomised placebo-controlled study. Lancet. 2007;370(9586):504-10.
3. Vockley J, Andersson HC, Antshel KM, et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014 Feb;16(2):188-200.
4. Javygtor prescribing information. Dr. Reddys Laboratories Inc. Princeton, NJ. May 2022.

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End Notes

1. All patients who are treating phenylketonuria (PKU) with sapropterin should also be treated with a phenylalanine (Phe) restricted diet [1].
2. Sapropterin was evaluated in a phase III, randomized, placebo-controlled trial to determine its efficacy in reducing blood Phe concentration [2]. The primary endpoint was mean change from baseline in concentration of Phe in blood after 6 weeks. The mean age was 20 years. Results showed that after 6 weeks of therapy, patients who received sapropterin (n=41) had a decrease in mean blood Phe of 236 micromol/L, compared with a 3 micromol/L increase in the placebo group (n=47; p less than 0.0001).
3. Patients should be evaluated for response to therapy after treatment with saproterin at 20mg/kg per day for a period of one month [1]. The 2 month initial authorization duration allows for patients who start on 10mg/kg per day for the first month, to increase their dose to 20mg/kg per day for an additional month prior to evaluation of response.
4. In clinical trials, response to therapy was defined as greater than or equal to 30% decrease in blood Phe from baseline [1]. The American College of Medical Genetics and Genomics guideline notes a significant decline in blood Phe is expected in sapropterin responders once treatment is started [3]. A reduction of 30% is most often cited in the literature as evidence of effective Phe reduction.
5. Phe blood levels should be checked after one week of sapropterin treatment and periodically after that to assess blood Phe control [1].

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Revision History

• 2024-10-02: 2024 Annual Review. Added trial of generic sapropterin to reauthorization criteria for Kuvan and Javygtor. Updated references.
• 2023-10-02: Annual Review
• 2022-11-02: Program Update
• 2022-09-28: Annual Review
• 2021-09-27: Annual Review
• 2021-04-14: Updated guideline to account for new GPIs for Brand Kuvan and generic sapropterin tablet formulation due to GPI replication.
• 2021-03-04: Updated criteria for Brand Kuvan to require a step through generic generic sapropterin.
• 2020-09-30: Annual Review: added generic sapropterin as target and updated references

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