CurrentViva HealthPolicy N/A

Avlayah (tividenofusp alfa-eknm) intravenous therapy for Hunter syndrome (MPS II)

Defines prior authorization, dosing, eligibility and renewal criteria for Avlayah (tividenofusp alfa-eknm) used to treat mucopolysaccharidosis II (Hunter syndrome) for Viva Health members; applies to clinicians ordering the drug and to claims review.

Policy Summary

PayerViva Health

PolicyAvlayah (tividenofusp alfa-eknm) intravenous therapy for Hunter syndrome (MPS II)

Policy CodePolicy N/A

Change TypeNo material change

Effective Date05/05/2026

Next Review Date

Key ActionObtain prior authorization (issued for 12 months) when member meets criteria including weight ≥5 kg, documented baseline measures, and definitive diagnosis of MPS II.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthsinitial prior authorization validity

1,800 mg/7dmax units

>=5 kgmin member weight

J3590HCPCS code

E76.1covered diagnosis

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Initial Therapy

Covered when ALL of the following are met

Initial Approval Criteria: Member weighs at least 5 kg; AND documented baseline age-appropriate values for one or more specified measures: for members ≥5 years: 6-minute walk test (6MWT), percent predicted forced vital capacity (FVC), joint range of motion, left ventricular hypertrophy, growth, quality of life measure (CHAQ/HAQ/MPS HAQ), and/or urinary glycosaminoglycan (uGAG)/urinary heparan sulfate (uHS); OR for members <5 years: spleen volume, liver volume, FVC, 6-MWT, and/or uGAG/uHS; AND note that for very young members in which FVC or 6-MWT are not suitable, requests will be reviewed on a case-by-case basis.

Requests for very young members where FVC/6-MWT are not suitable will be reviewed case-by-case.

Diagnostic Confirmation: Definitive diagnosis of MPS II confirmed by either deficient or absent iduronate 2-sulfatase (I2S) enzyme activity in white cells, fibroblasts, or plasma with normal activity of at least one other sulfatase; OR detection of pathogenic or likely pathogenic variants in the IDS gene by molecular genetic testing.

Renewal Criteria

Renewal when ALL of the following are met

Continuation and Safety: Member continues to meet the universal and other indication-specific relevant criteria identified for initial approval; AND absence of unacceptable toxicity from the drug (examples include severe hypersensitivity, severe infusion-associated reactions, severe anemia, membranous nephropathy); AND demonstration of beneficial response to therapy compared to pretreatment age-appropriate baseline in one or more specified measures: for members ≥5 years: stabilization or improvement in percent predicted FVC and/or 6-MWT, increased joint range of motion, decreased left ventricular hypertrophy, improved growth, improved quality of life (clinically meaningful change in CHAQ/HAQ/MPS HAQ), and/or reduction in uGAG/uHS levels; OR for members <5 years: reductions in spleen and/or liver volume, stabilization/improvement in FVC and/or 6-MWT, and/or reduction in uGAG/uHS levels.

Universal Criteria

Universal restrictions

Combination and monitoring: Not to be used in combination with other enzyme replacement therapies indicated for the treatment of Hunter Syndrome; AND obtain member hemoglobin prior to initiation, at 3 months after initiation, and periodically thereafter as clinically indicated; AND assess serum creatinine and urinary protein:creatinine ratio and monitor for development of membranous nephropathy throughout therapy.

Use of this therapy in combination with other enzyme replacement therapies indicated for the treatment of Hunter Syndrome is excluded. In addition, members must have baseline and ongoing laboratory monitoring: obtain hemoglobin prior to initiation, at approximately 3 months after initiation, and periodically thereafter as clinically indicated; monitor serum creatinine and urine protein:creatinine ratio and watch for development of membranous nephropathy during treatment.

Confirmation of diagnosis of MPS II via molecular genetic testing of the IDS gene

Detection of pathogenic or likely pathogenic variants in IDS qualifies as diagnostic confirmation for coverage.

Molecular confirmation: Molecular genetic testing of the IDS gene demonstrating pathogenic or likely pathogenic variant(s) qualifies as definitive diagnostic confirmation of MPS II for coverage purposes.

Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required (Initial)

Prior authorization (initial) — Prior authorization is required and will be issued for 12 months (365 days) when initial criteria are met.

Initial prior authorization validity: 12 months (365 days).
Member must weigh ≥ 5 kg at initiation.
Documented baseline age-appropriate measures as applicable: for members ≥5 years: 6-minute walk test (6MWT), percent predicted forced vital capacity (FVC), joint range of motion, left ventricular hypertrophy assessment, growth, quality of life measure (CHAQ/HAQ/MPS HAQ), and/or urinary glycosaminoglycan (uGAG)/urinary heparan sulfate (uHS); for members <5 years: spleen volume, liver volume, FVC, 6-MWT, and/or uGAG/uHS. Requests for very young members where FVC or 6-MWT are not suitable will be reviewed case-by-case.

Denial Risk

Combination Therapy Restriction

Combination therapy restriction — Therapy must not be used in combination with other enzyme replacement therapies indicated for Hunter syndrome.

Disallowed combination: any other enzyme replacement therapy for Hunter syndrome (e.g., idursulfase).

Documentation Required

Required Diagnostic and Baseline Documentation

Required diagnostic and baseline documentation — Provide documentation of definitive diagnosis of MPS II and baseline assessments prior to initiation.

Definitive diagnosis of MPS II confirmed by one of the following: deficient or absent iduronate 2-sulfatase (I2S) enzyme activity in white cells, fibroblasts, or plasma with normal activity of at least one other sulfatase; OR detection of pathogenic or likely pathogenic variants in the IDS gene by molecular genetic testing.
Baseline documentation as noted under initial criteria (age-appropriate measures such as 6-MWT, FVC, organ volumes, uGAG/uHS, joint range of motion, growth, quality of life index).

Documentation Required

Required Baseline and Ongoing Monitoring

Required baseline and ongoing monitoring — Labs and clinical monitoring must be obtained prior to initiation and at specified intervals thereafter to monitor for toxicity and effectiveness.

Obtain hemoglobin prior to initiation, at 3 months after initiation, and periodically thereafter as clinically indicated.
Assess serum creatinine and urine protein-to-creatinine ratio prior to initiation and monitor periodically during therapy to evaluate for signs of membranous nephropathy; monitor for development of membranous nephropathy throughout therapy.
Document clinical measures used to evaluate response (e.g., FVC, 6-MWT, organ volumes, uGAG/uHS, joint range of motion, growth, quality of life indices) and provide during renewal reviews.

Denial Risk

Contraindicated Combinations / Toxicity

Contraindicated combinations / toxicity — Do not continue therapy if used in combination with other enzyme replacement therapies for Hunter syndrome or if unacceptable toxicity occurs.

Contraindicated combination: concurrent use with other enzyme replacement therapies indicated for Hunter syndrome (e.g., idursulfase).
Unacceptable toxicity examples that warrant discontinuation/deny renewal: severe hypersensitivity including anaphylaxis, severe infusion-associated reactions (e.g., angioedema, hypotension, tachycardia, severe urticaria), severe anemia, membranous nephropathy, or other severe adverse events.
Renewal requires absence of unacceptable toxicity and demonstration of benefit compared to pretreatment baseline measures.

Eligibility Requirements

Members are eligible for therapy only when a definitive diagnosis of MPS II (Hunter syndrome) has been confirmed by one of the following: either deficient or absent iduronate 2-sulfatase (I2S) enzyme activity in white cells, fibroblasts, or plasma with normal activity of at least one other sulfatase, OR detection of pathogenic or likely pathogenic variants in the IDS gene by molecular genetic testing. Prior authorization is required and will be issued when the diagnostic confirmation and required baseline documentation and monitoring are provided. Additionally, therapy must not be initiated in combination with other approved enzyme replacement therapies for Hunter Syndrome, and baseline hemoglobin, serum creatinine, and urine protein:creatinine ratio should be documented as indicated.

Background

Mucopolysaccharidosis II (Hunter syndrome; MPS II) is an X-linked lysosomal storage disorder caused by deficiency of iduronate 2-sulfatase (I2S). Diagnostic confirmation can be established by biochemical assay demonstrating deficient or absent I2S activity in white cells, fibroblasts, or plasma (with normal activity of at least one other sulfatase) or by identifying pathogenic or likely pathogenic variants in the IDS gene via molecular genetic testing. Enzyme replacement therapies are used to replace deficient enzyme activity and clinical monitoring typically includes functional measures (for example, 6‑minute walk test and percent predicted FVC), joint range of motion, organ volumes, and urinary glycosaminoglycans; safety monitoring includes hemoglobin, renal function, and surveillance for membranous nephropathy. Therapy must not be used concomitantly with other enzyme replacement therapies for Hunter syndrome.

OpenPayer

Avlayah (tividenofusp alfa-eknm) intravenous therapy for Hunter syndrome (MPS II)

Coverage Criteria

Coding and Billing

Provider Actions and Documentation Requirements

Definitions

Covered Indications

Eligibility Requirements

Background