ModifiedCentenePolicy N/A

Lonafarnib (Zokinvy) coverage criteria for Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies

Defines Centene medical necessity criteria, dosing limits, and coverage rules for lonafarnib (Zokinvy) for treatment of Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies in eligible members.

Policy Summary

PayerCentene

PolicyLonafarnib (Zokinvy) coverage criteria for HGPS and processing-deficient progeroid laminopathies

Policy CodePolicy N/A

Change TypeDiagnostic and specialist requirement updatesBSA and dosing/approval duration aligned with FDA labeling

Effective DateNov 20, 2020

Next Review DateFeb 25, 2025

Key ActionSubmit prior authorization with genetic testing and clinical documentation; prescriptions must be from or in consultation with a geneticist, metabolic disorder specialist, or progeria specialist.

SourceLink

POLICY UPDATE CHANGES

Diagnostic criteria were revised to reflect FDA labeling and specialist requirement was changed from pediatrician/orthopedist/cardiologist to geneticist/metabolic disorder specialist/progeria specialist.

≥ 12 monthsminimum age for FDA indication

≥ 0.39 m2minimum BSA

4 monthsinitial approval

12 monthscontinuation approval

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Coverage Criteria for Lonafarnib (Zokinvy)

inv-01: Initial Approval

Covered when ALL of the following are met

Initial approval criteria for lonafarnib: 1) Diagnosis of one of the following: (a) Hutchinson-Gilford progeria syndrome (HGPS) with documentation of a pathogenic LMNA mutation (heterozygous LMNA mutation with progerin-like protein accumulation) OR (b) Processing-deficient progeroid laminopathy with documentation of homozygous or compound heterozygous ZMPSTE24 mutations; 2) Age ≥ 1 year; 3) Body surface area (BSA) ≥ 0.39 m2; 4) Prescribed by or in consultation with a geneticist, metabolic disorder specialist, or progeria specialist; 5) Initial dosing is BSA-based: starting dose 115 mg/m2 twice daily for 4 months with total daily dose rounded to the nearest available capsule and not to exceed maintenance maximum during the initial period; 6) Dose limits: initial-period daily dose rounded to nearest 25 mg per dosing table and maintenance maximum 300 mg/day; Approval duration: New starts — 4 months; Maintenance — 12 months.age >= 1 year; BSA >= 0.39 m2; initial dose 115 mg/m2 twice daily; max 300 mg/day

Provider must submit supporting documentation such as genetic testing and clinical notes; total daily dose to be rounded to nearest capsule strength per dosing table.

inv-02: Continuation (Renewal) Therapy

Covered when ALL of the following are met

Continuation therapy criteria: 1) Member is currently receiving medication via the Centene benefit or has previously met initial approval criteria; 2) Member is responding positively to therapy; 3) If the request is for a dose increase, the new total daily dose does not exceed 300 mg/day (rounded to the nearest available capsule per dosing table); Approval duration: 12 months.max 300 mg/day

Continuity of care provisions apply where state/product regulations require; documentation of clinical response should be submitted.

inv-03: Updated coverage criteria (summary)

Policy updated to align with FDA labeling; criteria include diagnostic and specialist requirements, minimum BSA, and dosing/approval duration adjustments.

FDA-aligned criteria: Diagnostic criteria revised to reflect FDA labeling (HGPS defined by heterozygous LMNA mutation with progerin-like protein accumulation and processing-deficient progeroid laminopathies defined by ZMPSTE24 mutations); specialist prescriber requirement updated to geneticist, metabolic disorder specialist, or progeria specialist; minimum BSA requirement added (BSA ≥ 0.39 m2); initial lower BSA‑based dosing and initial approval duration revised to 4 months; maintenance approval duration 12 months; maximum daily dose 300 mg/day.BSA >= 0.39 m2; initial 115 mg/m2 twice daily for 4 months; max 300 mg/day

See dosing tables and prescribing information for rounding to nearest capsule and required documentation.

Coverage is not authorized for other progeroid syndromes and for processing-proficient progeroid laminopathies. Requests for non‑FDA approved indications that are not addressed in this policy are also not authorized unless the request includes sufficient documentation of efficacy and safety and is supported under the applicable off‑label use policies (commercial: CP.CPA.09; health insurance marketplace: HIM.PA.154; Medicaid: CP PMN.53) or other evidence of coverage documents.

Per the prescribing information and the policy revision history, other progeroid syndromes (processing‑proficient progeroid laminopathies) are specifically noted as not coverable. The policy language and updates reflect alignment with the product labeling that excludes these syndromes from coverage.

Use of lonafarnib for non‑FDA approved indications or for progeroid syndromes not listed in this policy is considered not covered unless the provider supplies adequate supporting documentation demonstrating efficacy and safety and the request is approved under the referenced off‑label/non‑formulary policies noted in the policy (CP.CPA.09, HIM.PA.154, CP PMN.53) or other applicable evidence of coverage guidance.

The prescribing information and policy revisions explicitly state that use of lonafarnib for progeroid syndromes other than Hutchinson‑Gilford progeria syndrome — categorized as processing‑proficient progeroid laminopathies — is not coverable. Requests for these diagnoses will be denied unless coverage is supported by the referenced labeling or off‑label review processes.

Coding, Dosing and Key Numeric Criteria

Body Surface Area (BSA) and Dosing

Minimum BSA for initiationBody surface area (BSA) ≥ 0.39 m2 required for initiation of therapy

Initial BSA-based starting dose115 mg/m2 twice daily for the initial 4-month period

Maintenance BSA-based dose150 mg/m2 twice daily for maintenance dosing after initial period

Total daily dosing and roundingTotal daily dose rounded to nearest available capsule strength per dosing tables; morning and evening doses determined by rounded total

Maximum daily doseMaximum dose 300 mg/day

Initial Approval Duration

Provider Actions, Prior Authorization and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Zokinvy. Initial approvals for new starts are granted for 4 months; maintenance/continuation approvals are granted for 12 months. Initial dosing for new starts follows a lower BSA‑based regimen (115 mg/m2 twice daily) for the first 4 months, with a maintenance BSA‑based regimen (150 mg/m2 twice daily) thereafter. Maximum total daily dose is 300 mg/day. Requests must specify indication, dosing, and duration.

Initial approval duration: 4 months (new starts)
Maintenance approval duration: 12 months
Initial dosing: 115 mg/m2 twice daily for first 4 months
Maintenance dosing: 150 mg/m2 twice daily thereafter
Maximum dose: 300 mg/day

Step Therapy

Step Therapy / Formulary Routing

No specific step therapy sequence is required for approval of Zokinvy under this policy. Coverage routing and any utilization controls for formulary, non‑formulary, or off‑label uses defer to the line‑of‑business policies referenced below.

Background

Hutchinson‑Gilford progeria syndrome (HGPS) is a rare, pediatric genetic disorder characterized by features of accelerated aging beginning in childhood. It is caused by pathogenic variants in LMNA that lead to production of the abnormal protein progerin, which results in severe growth deficiency, characteristic craniofacial and musculoskeletal features, and early‑onset cardiovascular disease. Lonafarnib (Zokinvy) is indicated to reduce the risk of mortality in HGPS and to treat processing‑deficient progeroid laminopathies when labeled criteria are met.

Definitions

Hutchinson‑Gilford Progeria Syndrome (HGPS)

DefinitionHutchinson-Gilford progeria syndrome (HGPS) is established by characteristic clinical features and identification of a heterozygous pathogenic LMNA variant that results in production of abnormal lamin A protein (progerin)

Clinical featuresFeatures include profound growth deficiency in the first year, characteristic facial features, musculoskeletal abnormalities, and early-onset cardiovascular disease

Diagnostic basisDiagnosis based on characteristic clinical presentation plus genetic testing identifying a heterozygous LMNA pathogenic variant

Processing‑Deficient Progeroid Laminopathy

DefinitionProcessing‑deficient progeroid laminopathy refers to progeroid laminopathies due to homozygous or compound heterozygous ZMPSTE24 mutations or heterozygous LMNA mutations with progerin‑like protein accumulation

Indication for therapy