CurrentBlue Cross Blue Shield - IowaPolicy 05.04.28

Zokinvy (lonafarnib) — coverage criteria

Defines prior authorization, medical necessity, dosing, and coverage criteria for Zokinvy (lonafarnib) for treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies for Wellmark members.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyZokinvy (lonafarnib) — coverage criteria

Policy CodePolicy 05.04.28

Change TypeAdministrative review (no material clinical changes)

Effective Date

Next Review Date

Key ActionSubmit prior authorization with genetic confirmation of HGPS or processing-deficient progeroid laminopathy, documentation of BSA ≥ 0.39 m2, age ≥ 12 months, and dosing appropriate for BSA.

SourceLink

POLICY UPDATE CHANGES

Policy reviewed January 2026 with current effective date March 7, 2025 and prior revision January 2025.

12 monthsapproval duration

≥12 momin age

≥0.39 m2min BSA

120 caps/30dmax qty

63treated pts (safety)

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3 mo–2.5 yrmedian lifespan increase

Coverage Criteria

inv-01: Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met

Initial approval criteria: 1) Genetic confirmation of diagnosis: Hutchinson-Gilford progeria syndrome (HGPS) OR processing-deficient progeroid laminopathy defined as either (a) heterozygous LMNA mutation with progerin-like protein accumulation OR (b) homozygous or compound heterozygous ZMPSTE24 mutation (confirmed by genetic testing); 2) Member is 12 months of age or older; 3) Medication is prescribed by, or in consultation with, a specialist in progeria treatment; 4) Body surface area (BSA) ≥ 0.39 m2 as documented in medical records; 5) Dosage ordered is appropriate for the patient's BSA.

inv-02: Continuation Therapy — Continuation criteria — all initial criteria plus tolerance

Continuation criteria — all initial criteria plus tolerance

Continuation approval criteria: Member meets all initial approval criteria AND is tolerating therapy with the requested medication.

Approval duration: 12 months.

inv-03: Initial therapy — Covered when ALL of the following are met

Covered when ALL of the following are met

Indication: Patient has a diagnosis of Hutchinson-Gilford progeria syndrome (HGPS) or a processing-deficient progeroid laminopathy (PL).

Supported by FDA approval and clinical rationale in document.

Rationale/Evidence: Clinical benefit demonstrated by an Observational Cohort Survival Study comparing treated patients to matched untreated natural history cohort; treated cohort (n=62) showed median lifespan increase (average +3 months at 3 years follow-up and average +2.5 years through last follow-up up to 11 years).

Includes pooled treated patients from Study 1 and Study 2.

Coverage will not be provided for members with other progeroid syndromes or processing-proficient progeroid laminopathies. These diagnoses are explicit exclusions from authorization for Zokinvy (lonafarnib).

Zokinvy (lonafarnib) is contraindicated with concurrent use of strong or moderate CYP3A inhibitors or inducers. Concurrent use with midazolam, lovastatin, simvastatin, and atorvastatin is also contraindicated and may result in denial of therapy if the requested treatment would violate these drug interaction restrictions.

Zokinvy is considered not medically necessary for members who do not meet the specified initial or continuation criteria. Members already receiving samples or enrolled in the manufacturer's patient assistance program must meet the initial approval criteria to continue receiving coverage.

Initial Therapy Criteria

inv-26: Initial Therapy — Initial approval criteria for Zokinvy

Initial approval criteria for Zokinvy

Genetic diagnosis: Genetic testing confirming one of: (a) Hutchinson-Gilford progeria syndrome (HGPS) OR (b) processing-deficient progeroid laminopathy defined as heterozygous LMNA mutation with progerin-like accumulation OR homozygous/compound heterozygous ZMPSTE24 mutation.

Required documentation for initiation must include genetic test results.

Age: Member is ≥ 12 months of age.≥ 12 months

Prescriber: Medication prescribed by, or in consultation with, a specialist in progeria treatment.

Continuation Therapy Criteria

inv-28: Continuation Therapy — requires prior criteria met and tolerated therapy and appropriate dosing for BSA

Continuation requires prior criteria met and tolerated therapy and appropriate dosing for BSA

Continuation: Member meets all initial approval criteria AND documentation supports that the member is on an appropriate dosage for the member's body surface area AND member is tolerating therapy.

Approval granted for 12 months; continuation documentation should include dosing appropriate for BSA.

Dosing verification: Total daily dosage documented and rounded to the nearest 25 mg with capsule counts consistent with 50 mg and 75 mg strengths as applicable.Total daily dose rounded to nearest 25 mg

Refer to Dosage and Administration for capsule equivalents.

inv-29: Continuation therapy — supported by long-term follow-up in extension studies

Continuation therapy supported by long-term follow-up and safety data

Coding and Dosage Details

Billing and procedure codesmixed

N/A	No specific CPT/HCPCS/Revenue/ICD codes provided in this section; providers instructed to use appropriate codes

inv-08: Body Surface Area (BSA) — >= 0.39 m2

ThresholdBody surface area (BSA) ≥ 0.39 m2

Source contextRequired for initiation and listed among initial approval criteria

DocumentationMedical records must document BSA ≥ 0.39 m2 for prior authorization

inv-09: Minimum age — >= 12 months

Minimum agePatients must be ≥ 12 months of age

Indication alignmentAge requirement is consistent with FDA-approved indication

Authorization note

Provider Actions and Requirements

Prior Authorization

Prior authorization requirements

Prior authorization requires genetic confirmation of diagnosis (HGPS or a processing-deficient progeroid laminopathy), member age ≥ 12 months, body surface area (BSA) ≥ 0.39 m2, prescription by or in consultation with a progeria specialist, and dosage appropriate for the patient's BSA. Approval duration is 12 months.

Genetic confirmation: HGPS OR processing-deficient progeroid laminopathy (heterozygous LMNA with progerin-like accumulation OR homozygous/compound heterozygous ZMPSTE24 mutation).
Minimum age: ≥ 12 months.
BSA requirement: ≥ 0.39 m2.
Medication prescribed by or in consultation with a specialist in progeria treatment.
Dosage must be appropriate for patient's BSA.

Quantity Limits and Dispensing

inv-30: Zokinvy (lonafarnib) — Maximum 120 capsules

Maximum quantityMaximum 120 capsules per 30 days

BasisQuantity limit varies by BSA; maximum based on BSA is 120 capsules per 30 days

Policy locationQuantity Limits Apply section

inv-31: Zokinvy (lonafarnib) — total daily dosage rounded to nearest 25 mg; capsule counts per 50 mg and 75 mg strengths

Total daily dosage roundingTotal daily dose is rounded to the nearest 25 mg

Capsule strengthsAvailable strengths referenced: 50 mg and 75 mg capsules (capsule counts provided per strength in Dosage and Administration)

Definitions

inv-22: Processing-deficient progeroid laminopathy — definition and genetic basis

DefinitionA processing-deficient progeroid laminopathy is caused by mutations resulting in processing-deficient, permanently farnesylated proteins (e.g., heterozygous LMNA with progerin-like accumulation or homozygous/compound heterozygous ZMPSTE24 mutations)

Genetic basisIncludes heterozygous LMNA mutations with progerin-like protein accumulation or homozygous/compound heterozygous ZMPSTE24 mutations

Pathogenic mechanismMutant proteins are permanently farnesylated leading to accumulation implicated in disease pathogenesis

inv-23: HGPS (Hutchinson-Gilford progeria syndrome) — definition and LMNA mutation cause

DefinitionHutchinson-Gilford progeria syndrome (HGPS) is a rare genetic premature aging disease caused by a point mutation in LMNA resulting in production and permanent farnesylation of progerin

Background

Hutchinson‑Gilford progeria syndrome (HGPS) and related progeroid laminopathies (PLs) are rare, genetic disorders characterized by premature aging and early mortality, most commonly from arteriosclerotic cardiovascular events. HGPS is typically caused by a point mutation in the LMNA gene that produces permanently farnesylated progerin; some processing‑deficient PLs arise from LMNA or ZMPSTE24 mutations that similarly lead to accumulation of permanently farnesylated mutant proteins. Zokinvy (lonafarnib) is an oral farnesyltransferase inhibitor intended to prevent accumulation of these aberrant proteins and is the first FDA‑approved therapy for HGPS and certain processing‑deficient progeroid laminopathies. Clinical safety data include 63 treated patients (median treatment duration 2.2 years), and efficacy evidence is derived from an observational cohort survival analysis comparing treated patients to matched untreated natural history cohorts.

Site of Care

Note

Oral administration — home

Zokinvy is administered orally and may be taken at home; the policy does not specify any site‑of‑care restrictions.

Oral administration—no site restrictions specified (home acceptable).

Revision History

March 12, 2021original_effective_date

Policy originally effective.

January 2025revision

Policy revised in January 2025.

March 7, 2025current_effective_date

Current policy effective date updated to March 7, 2025.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyZokinvy (lonafarnib) — coverage criteria

Policy CodePolicy 05.04.28

Change TypeAdministrative review (no material clinical changes)

Effective Date

Next Review Date

SourceLink

On This Page

Body surface area: Member has documented BSA ≥ 0.39 m2.≥ 0.39 m2

Medical records (e.g., chart notes, laboratory values) must document BSA.

Dosage: Ordered dosage is appropriate for the patient's BSA.

Dosage rounding: total daily dose rounded to nearest 25 mg (see Dosage and Administration).

inv-27: Initial therapy — Initial dosing and evidence summary

Initial dosing and evidence summary

Dose reference: Recommended dosage referenced in trials and recommended dosing uses 150 mg/m2 (recommended dosage during trials); total daily dosage should be rounded to the nearest 25 mg and capsule counts follow 50 mg and 75 mg strengths as described in Dosage and Administration.150 mg/m2

See Dosage and Administration for capsule count and rounding guidance.

Evidence summary: Efficacy evidence based on Observational Cohort Survival Study (pooled treated n=62) comparing treated HGPS patients to matched untreated natural history cohort; median lifespan increased on average by 3 months at 3-year follow-up and by 2.5 years through last follow-up (up to 11 years). Safety evaluated in 63 patients with median exposure 2.2 years; common adverse reactions and contraindicated concomitant medications are documented.

Safety: evaluated in 63 patients; common adverse reactions listed in clinical rationale.

Long-term follow-up: Patients continuing on Zokinvy received therapy in study phases for multiple years (up to 5 years in extension and up to 11 years follow-up reported for some patients).

Continuation is supported by survival and safety data from clinical studies and extensions.

Safety support: Safety evaluated in 63 patients with median duration of exposure 2.2 years (1.9 years at recommended 150 mg/m2); common adverse reactions and contraindications are described and should be considered when authorizing continuation.

Concurrent use with strong/moderate CYP3A inhibitors/inducers and certain statins and midazolam is contraindicated.

Prior authorization requires documentation of age ≥ 12 months

inv-10: Total daily dosage rounding — rounded to nearest 25 mg

Rounding ruleTotal daily dosage rounded to the nearest 25 mg

Dosage calculationCapsule counts and dosing tables use rounded total daily dose for administration

Reference sectionSee Dosage and Administration for rounding and capsule count details

Billing Rule

Billing and coding submission

Providers must submit appropriate CPT, HCPCS, revenue, and/or ICD diagnostic codes when reporting services; the policy does not list specific billing codes in this section (N/A).

Use appropriate CPT, HCPCS (alpha-numeric), revenue, and/or ICD codes as applicable for provider services.

Step Therapy

Step therapy / program note

No step therapy program is specified for Zokinvy. Members currently receiving samples or therapy via the manufacturer's patient assistance program must still meet the initial approval criteria to continue coverage.

Samples or patient assistance program (PAP) recipients are required to meet initial approval criteria.

Step Therapy

Step therapy not specified

There are no step therapy sequences described; Zokinvy is identified as the first and only FDA‑approved treatment for HGPS and certain processing-deficient progeroid laminopathies.

Zokinvy is the first and only FDA‑approved treatment for HGPS and some PLs.

Documentation Required

Required documentation for initiation

For initiation, submit documentation of genetic testing confirming HGPS or a processing-deficient progeroid laminopathy and medical records documenting a body surface area (BSA) ≥ 0.39 m2.

Genetic test results showing HGPS OR processing-deficient PL (heterozygous LMNA with progerin-like accumulation OR homozygous/compound heterozygous ZMPSTE24 mutation).
Medical records/chart notes documenting BSA ≥ 0.39 m2.

Documentation Required

Required documentation for continuation

For continuation requests, provide documentation that the member is receiving an appropriate dosage for the member's body surface area.

Records or dosing documentation showing dose is appropriate for the member's BSA.

Documentation Required

Diagnosis and genetic documentation

Documentation must support the diagnosis of HGPS or a processing-deficient progeroid laminopathy and include genetic mutation information and relevant prior natural history or treatment status.

Genetic mutation details (LMNA or ZMPSTE24) confirming the specified diagnosis.
Clinical history or prior treatment/natural history relevant to matching treated patients to natural history cohorts.

Denial Risk

Exclusion — non-covered progeroid syndromes

Coverage will not be provided for members with other progeroid syndromes or processing‑proficient progeroid laminopathies; such cases are excluded from coverage.

Exclude members diagnosed with other progeroid syndromes or processing‑proficient progeroid laminopathies.

Denial Risk

Not medically necessary if criteria not met

Zokinvy is considered not medically necessary when the specified initial or continuation criteria are not met; therapy may be denied if documentation does not satisfy the policy requirements.

Denial risk if genetic confirmation, age, BSA, specialist involvement, or appropriate dosing criteria are not documented.

Denial Risk

Contraindicated drug interactions

Concurrent use of Zokinvy with strong or moderate CYP3A inhibitors or inducers, midazolam, lovastatin, simvastatin, or atorvastatin is contraindicated and may lead to denial if therapy would violate this contraindication.

Do not co-administer strong or moderate CYP3A inhibitors or inducers with Zokinvy.
Avoid concurrent use with midazolam, lovastatin, simvastatin, and atorvastatin.

Quantity linkQuantity limits vary by BSA and reference the rounded total daily dose when determining capsule counts

Genetic causeTypically due to a point mutation in the lamin A/C gene (LMNA) leading to progerin production

Clinical consequenceLeads to premature widespread arteriosclerosis and early mortality (e.g., myocardial infarction or stroke)

inv-24: HGPS — concise label entry

LabelHGPS

Short definitionHutchinson-Gilford progeria syndrome — rare premature aging disease due to LMNA mutation producing progerin

Use in policyListed as an indication for Zokinvy when genetically confirmed

inv-25: Progeroid laminopathies — concise label entry

LabelProgeroid laminopathies (PLs)

Short definitionProcessing-deficient laminopathies caused by mutations in LMNA and/or ZMPSTE24 producing permanently farnesylated mutant proteins distinct from progerin

Policy relevanceCertain PLs are indications for Zokinvy when genetic confirmation shows processing-deficient mutations

Policy reviewed (administrative update noted).