ModifiedmhnPolicy CP.PHAR.283

Clinical Policy: Lomitapide (Juxtapid)

Defines medical necessity, prior authorization, and coverage criteria for lomitapide (Juxtapid) for members with homozygous familial hypercholesterolemia and related administrative guidance for clinicians and payers.

Policy Summary

Payermhn

PolicyLomitapide (Juxtapid) coverage

Policy CodePolicy CP.PHAR.283

Change TypeMaterial updates and criteria clarifications (2024–2025)

Effective DateOct 1, 2016

Next Review Date

Key ActionSubmit prior authorization with clinical documentation showing HoFH diagnosis, recent LDL‑C, statin adherence, and that the treatment plan excludes coadministration with Leqvio, Repatha, or Praluent.

SourceLink

POLICY UPDATE CHANGES

Added Leqvio to the list of drugs where coadministration is not allowed and required that the treatment plan not include coadministration with Leqvio, Repatha, or Praluent for both initial and continued therapy.

Lowered minimum untreated LDL requirement to 400 mg/dL and revised evidence of familial hypercholesterolemia to require evidence in at least one parent.

Added requirement for adherence to statin therapy on re-authorization.

60 mg/daymaximum daily dose allowed

2maximum capsules per day

6 monthsinitial approval duration

≥18

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Coverage Criteria for Lomitapide (Juxtapid)

inv-01: Initial Therapy — Homozygous Familial Hypercholesterolemia

Covered when ALL of the following are met for HoFH:

Diagnosis of HoFH: Diagnosis of homozygous familial hypercholesterolemia (HoFH) defined by ONE of: (a) genetic mutation indicating HoFH (e.g., LDLR, PCSK9, apoB, LDLRAP1); (b) treated LDL-C ≥ 300 mg/dL or non-HDL-C ≥ 330 mg/dL; (c) untreated LDL-C ≥ 400 mg/dL PLUS either (i) tendinous or cutaneous xanthoma prior to age 10 years or (ii) evidence of familial hypercholesterolemia in at least one parent.

Prescriber: Prescribed by or in consultation with a cardiologist, endocrinologist, or lipid specialist.

Age requirement: Patient is ≥ 18 years of age.

Recent LDL-C documented: Documentation of recent (within the last 60 days) LDL-C meeting one of: (a) ≥ 70 mg/dL or (b) ≥ 55 mg/dL if member has ASCVD and is at very high risk (see Appendix H).60 days

Concomitant statin if on statin: If patient is on statin therapy, Juxtapid must be prescribed with a statin at the maximally tolerated dose and the member must have been adherent to that regimen for at least the last 4 months (intensity and intolerance criteria per Appendix D and F).4 months adherence

Statin-intolerance pathway (if not on statin): If not on statin therapy, either (a) statin therapy is contraindicated per Appendix E OR (b) patient is statin intolerant with trial of at least two statins (one must be hydrophilic: pravastatin, fluvastatin, or rosuvastatin) and meets documented SAMS and rechallenge criteria.

Rechallenge and documentation requirements described in policy and Appendix G.

Ezetimibe trial: Member has been adherent to ezetimibe used concomitantly with a statin at the maximally tolerated dose for at least the last 4 months unless ezetimibe is contraindicated or intolerance is documented.4 months

PCSK9 inhibitor failure: Failure of a preferred PCSK9 inhibitor, if applicable, unless contraindicated or clinically significant adverse effects occurred.

Prior authorization may be required for PCSK9 inhibitors.

No coadministration with PCSK9/inclisiran: Treatment plan must not include coadministration with Leqvio (inclisiran), Repatha, or Praluent.

Dose limits: Dose must not exceed 60 mg per day and 2 capsules per day.60 mg/day; 2 caps/day

Approval duration: 6 months.

inv-02: Continuation Therapy — Homozygous Familial Hypercholesterolemia

Continuation Therapy — Homozygous Familial Hypercholesterolemia

Previous coverage or continuity: Member is currently receiving medication via Centene benefit or previously met initial approval criteria, or member is currently receiving medication and is enrolled in a state/product with continuity of care regulations.

Statin adherence if tolerant: If statin tolerant, documentation of adherence to a statin at the maximally tolerated dose is required.

Clinical response: Member is responding positively to therapy as evidenced by lab results within the last 3 months showing an LDL-C reduction since initiation of Juxtapid therapy.3 months

No coadministration: Treatment plan does not include coadministration with Leqvio, Repatha, or Praluent.

inv-03: Notable approval criteria updates

Policy updates and coverage constraints noted in annual reviews:

Coadministration exclusion: Treatment plan does not include coadministration with Leqvio, Repatha, or Praluent.

Added in 1Q 2024 and applied to both initial and continuation therapy.

Statin adherence for re-authorization: Documentation of adherence to statin therapy is required on re-authorization.

Requirement added in 1Q 2021 and carried forward.

Familial hypercholesterolemia evidence and untreated LDL threshold: Evidence of familial hypercholesterolemia in at least one parent and untreated LDL ≥ 400 mg/dL for certain approvals.untreated LDL ≥ 400 mg/dL

Lowered/clarified in 1Q 2025 review per 2022 ACC pathway updates.

Non‑FDA approved indications for lomitapide (Juxtapid) that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety according to the plan’s off‑label use policies (see CP.CPA.09 for commercial members and CP.PMN.53 for Medicaid).

Lomitapide (Juxtapid) distribution is restricted by a Risk Evaluation and Mitigation Strategy (REMS) program due to the risk of hepatotoxicity; prescribers and patients must comply with REMS enrollment and requirements. In addition, coadministration with Leqvio, Repatha, or Praluent is not allowed under this policy — treatment plans must exclude these agents for both initial and continuation therapy (Leqvio was added to the exclusion list in the 1Q 2024 update).

The safety and effectiveness of Juxtapid have not been established in patients who do not have homozygous familial hypercholesterolemia (HoFH), including those with heterozygous familial hypercholesterolemia (HeFH). Use in these populations is therefore not authorized under this policy. The policy updates also clarify familial‑hypercholesterolemia evidence requirements and untreated LDL thresholds as part of approval criteria changes.

Moderate or severe hepatic impairment (Child‑Pugh B or C) and active liver disease are important contraindications/contextual safety concerns: ezetimibe is contraindicated in moderate or severe hepatic impairment, and lomitapide carries a hepatotoxicity risk requiring REMS‑based distribution and monitoring. Statin safety in pregnancy has been updated by the FDA; clinicians should apply current statin safety guidance and consider hepatic status when co‑prescribing statins with lomitapide.

Laboratory Thresholds and Coding-Related Criteria

inv-08: LDL-C entry thresholds — treated LDL-C, non-HDL-C, untreated LDL-C and recent LDL-C requirements

Treated LDL-C entry thresholdTreated LDL-C ≥ 300 mg/dL

Non-HDL-C entry thresholdNon‑HDL‑C ≥ 330 mg/dL

Untreated LDL-C entry thresholdUntreated LDL‑C ≥ 400 mg/dL (can be used with early xanthoma or parental FH evidence)

Recent LDL-C requirementDocumentation of recent LDL‑C within 60 days: ≥ 70 mg/dL (or ≥ 55 mg/dL if ASCVD and very high risk)

inv-09: LDL thresholds — Minimum untreated LDL requirement changes and ASCVD very high risk thresholds

Minimum untreated LDL requirement (updated)Minimum untreated LDL requirement lowered to 400 mg/dL for certain approval pathways (per 1Q 2025/annual reviews)

Prior Authorization and Provider Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Juxtapid (lomitapide). Approval duration is 6 months.

Prior authorization (PA) required
Approval duration: 6 months

Documentation Required

Provider must submit documentation (office chart notes, lab results, specialist consultation notes) demonstrating the member meets all clinical criteria for HoFH and other policy requirements. Lack of adequate documentation may result in denial.

Submit office notes and recent laboratory results (including LDL-C within 60 days)
Specialist documentation if prescribed in consultation (cardiology, endocrinology, or lipid specialist)
Document statin and ezetimibe adherence or contraindication/intolerance as applicable

Initial Therapy Criteria and Safety Requirements

inv-23: Initial — HoFH

Initial approval criteria for HoFH (must meet all):

HoFH diagnosis: Diagnosis of HoFH per specified genetic, treated LDL-C/non-HDL-C thresholds, or untreated LDL-C plus early xanthoma or parental FH as defined in policy.

Specialist prescriber: Prescribed by or in consultation with a cardiologist, endocrinologist, or lipid specialist.

Age ≥ 18 years: Patient is age 18 years or older.

Recent LDL-C within 60 days: Documentation of recent LDL-C within the last 60 days meeting policy thresholds (≥70 mg/dL or ≥55 mg/dL if ASCVD and very high risk).

Criteria for Ongoing Therapy

inv-25: Continu — HoFH

Criteria for ongoing therapy continuation

Continuity or previous approval: Member is currently receiving medication via Centene benefit or previously met initial approval criteria, or is enrolled in a state/product with continuity of care regulations.

Clinical response: Documented LDL-C reduction within the last 3 months since initiation of Juxtapid therapy demonstrating continued response.3 months

Dose limits: Dose does not exceed 60 mg/day and 2 capsules/day.60 mg/day; 2 caps/day

Prior Trial and Step Therapy Requirements

Requirement	Details
Prior trial of a preferred PCSK9 inhibitor required
Failure of a preferred PCSK9 inhibitor is required, if applicable, unless contraindicated or clinically significant adverse effects are experienced

Requirement	Documentation needed
Document prior attempt/failure of preferred PCSK9 inhibitor when policy redirects to PCSK9 failure
Policy history notes redirection language revised to 'failure of a preferred PCSK9 inhibitor, if applicable' — documentation should show prior therapy trial and clinical reason for failure or contraindication

Quantity Limits and Dosing Caps

inv-29: Lomitapide (Juxtapid) — maximum daily dose (mg)

Maximum daily dose (mg)Maximum lomitapide (Juxtapid) dose = 60 mg/day

Titration noteStart 5 mg PO QD and titrate per schedule up to maximum 60 mg/day with specified intervals and monitoring

Dose adjustmentsModify dosing for CYP3A4 inhibitors, renal impairment, or baseline hepatic impairment; adjust if transaminases ≥ 3x ULN

inv-30: Lomitapide (Juxtapid) — maximum capsules per day

Maximum capsules per dayMaximum 2 capsules per day

Capsule strengths availableProduct availability: capsules in 5 mg, 10 mg, 20 mg, 30 mg

Distribution and Site-of-Care Requirements

Note

REMS distribution and hepatotoxicity monitoring required (specialty)

Juxtapid must be dispensed through the REMS program and monitoring for hepatotoxicity is required, consistent with REMS distribution and specialized outpatient care.

REMS program distribution is required due to hepatotoxicity risk.
Appropriate monitoring (e.g., liver transaminases) is implied in specialty/outpatient settings per REMS.

Background

Lomitapide is a microsomal triglyceride transfer protein inhibitor indicated as an adjunct to a low‑fat diet and other lipid‑lowering treatments (including LDL apheresis where available) to reduce LDL‑C, total cholesterol, apolipoprotein B, and non‑HDL‑C in patients with homozygous familial hypercholesterolemia (HoFH). Safety and effectiveness in patients without HoFH have not been established, and the effect on cardiovascular morbidity and mortality is undetermined. Because of hepatotoxicity risk, Juxtapid is available only through the Juxtapid REMS Program.

Definitions and Abbreviations

inv-19: HoFH definition — genetic mutation OR treated LDL-C ≥ 300 mg/dL or non-HDL-C ≥ 330 mg/dL.

HoFH diagnostic definition (genetic)Diagnosis of HoFH can be established by a genetic mutation indicating HoFH (e.g., LDLR, PCSK9, apoB, LDLRAP1)

HoFH diagnostic definition (treated LDL-C/non-HDL-C)Treated LDL‑C ≥ 300 mg/dL or non‑HDL‑C ≥ 330 mg/dL qualifies as HoFH per policy definition

HoFH diagnostic definition (untreated LDL-C)Untreated LDL‑C ≥ 400 mg/dL plus either tendinous/cutaneous xanthoma prior to age 10 or evidence of familial hypercholesterolemia in at least one parent

inv-20: SAMS — Statin-associated muscle symptoms abbreviation definition.

SAMS abbreviationSAMS = statin-associated muscle symptoms

Contextual appendix

Revision History and Policy Changes

2025-02-25annual_reviewLatest

Lowered untreated LDL requirement to 400 mg/dL and revised familial hypercholesterolemia evidence to require FH in at least one parent (1Q 2025 annual review).

2024-02-24annual_review

Added Leqvio to the list of drugs prohibited for coadministration and extended the 'no coadministration with Leqvio, Repatha, or Praluent' requirement into continuation criteria (1Q 2024 annual review).

2021-02-21

Policy Summary

Payermhn

PolicyLomitapide (Juxtapid) coverage

Policy CodePolicy CP.PHAR.283

Change TypeMaterial updates and criteria clarifications (2024–2025)

Effective DateOct 1, 2016

Next Review Date

SourceLink

On This Page

Dose limit on increase requests: If request is for a dose increase, new dose must not exceed 60 mg per day and 2 capsules per day.60 mg/day; 2 caps/day

ASCVD very high risk LDL thresholdFor members with ASCVD at very high risk, recent LDL‑C threshold lowered to ≥ 55 mg/dL (per 2022 ACC pathway reflected in 1Q 2023 review)

Reference to review historyPolicy changes reflect ACC guidance updates and annual reviews (see 1Q 2023 and 1Q 2025 notes)

Documentation Required

Clinical Documentation Requirements

Clinical documentation must include evidence of diagnosis and clinical criteria: genetic testing or LDL-C thresholds consistent with HoFH, recent LDL-C values (within 60 days), age ≥18 years, and prescriber specialty. For members on statins, provide documentation of maximally tolerated statin therapy and adherence for ≥4 months; for statin-intolerant members provide documentation of trials and re-challenge per policy.

Diagnosis of HoFH by genetic mutation OR treated LDL-C ≥300 mg/dL OR untreated LDL-C ≥400 mg/dL with qualifying signs/family history
Recent LDL‑C within last 60 days (≥70 mg/dL, or ≥55 mg/dL if ASCVD at very high risk)
Age ≥18 years
Prescribed by or in consultation with cardiologist, endocrinologist, or lipid specialist
Statin adherence evidence for last 4 months or documentation of contraindication/intolerance per Appendix E and statin trial/rechallenge details

Documentation Required

Dosing, Safety Monitoring, and REMS Documentation

Prior authorization requires documentation of dosing and safety monitoring consistent with the lomitapide titration schedule and REMS requirements. Provide information supporting dosing adjustments for CYP3A4 interactions, renal/hepatic impairment, and any transaminase elevations.

Dosing per titration schedule (starting 5 mg QD with escalation intervals: 5 mg QD ≥2 weeks, then 10/20/40 mg QD ≥4 weeks each up to max 60 mg/day)
Documentation of monitoring plan for hepatotoxicity and transaminases (per REMS)
Note modifications for concomitant CYP3A4 inhibitors, renal impairment, or baseline hepatic impairment

Prior Authorization

REMS Enrollment and Coadministration Restrictions; PCSK9 Step Requirement

Member must be enrolled in the Juxtapid REMS Program. Treatment must not include coadministration with Leqvio, Repatha, or Praluent. Prior use/failure of a preferred PCSK9 inhibitor is required when applicable unless contraindicated.

Enrollment in Juxtapid REMS Program required
No coadministration with Leqvio, Repatha, or Praluent
Failure of a preferred PCSK9 inhibitor required if applicable (document trial, duration, and reason for failure/ intolerance)

Step Therapy

Step Therapy / Redirection

Step therapy/redirection: where a preferred PCSK9 inhibitor is applicable, member must have failed that agent prior to approval of lomitapide unless there is a documented contraindication or clinically significant adverse effect. Providers should document trials, durations, and outcomes of preferred agents.

Redirection to preferred PCSK9 inhibitor failure required before lomitapide when applicable
If PCSK9 inhibitor is contraindicated, document reason

See Appendix H for very high risk definition.

Statin requirements (if on statin): If on statin therapy, Juxtapid must be used with a statin at the maximally tolerated dose and member adherence to that regimen for at least 4 months must be documented (intensity/intolerance criteria in Appendices D and F).4 months adherence

Statin contraindication/intolerance (if not on statin): If not on statin therapy, either statin therapy is contraindicated per Appendix E OR the member is statin intolerant after trials of at least two statins (one hydrophilic) with documented SAMS and appropriate rechallenge.

Rechallenge requirements per policy.

Ezetimibe adherence: Member has been adherent to ezetimibe concomitant with a statin at maximally tolerated dose for at least 4 months unless contraindicated or intolerant.4 months

PCSK9 inhibitor failure: Failure of a preferred PCSK9 inhibitor, if applicable, unless contraindicated or clinically significant adverse effects occurred.

Prior authorization may be required for PCSK9 inhibitors.

No coadministration with Leqvio/Repatha/Praluent: Treatment plan must not include coadministration with Leqvio, Repatha, or Praluent.

Dose limits: Dose must not exceed 60 mg/day and 2 capsules/day.60 mg/day; 2 caps/day

Approval duration: 6 months.

inv-24: Initial therapy dosing and safety

Initial therapy dosing and safety requirements

Initial dosing and titration: Start lomitapide 5 mg orally once daily and titrate per schedule: 5 mg for at least 2 weeks, then 10 mg, 20 mg, and 40 mg each for at least 4 weeks before escalation; escalate gradually based on safety and tolerability.max 60 mg/day

Modify dosing for concomitant CYP3A4 inhibitors, renal impairment, or baseline hepatic impairment; adjust if transaminases ≥ 3x ULN.

inv-26: Continuation of therapy

Continuation requires adherence and ongoing exclusion of disallowed coadministration; prior initial requirements apply to continuation.

No coadministration: Continued documentation that the treatment plan does not include coadministration with Leqvio, Repatha, or Praluent.

Requirement added in 1Q 2024 and applied to continuation.

Statin adherence at re-authorization: Evidence of adherence to a statin at maximally tolerated dose is required for re-authorization when the member is statin tolerant.

Added in 1Q 2021 and carried forward.

Continuation of initial requirements: Initial approval requirements (diagnosis, specialist involvement, LDL documentation, ezetimibe trial, PCSK9 failure when applicable, and dose limits) remain applicable during continuation.

Corresponding mg limit

2 capsules per day corresponds to dosing constraints and must not exceed 60 mg/day

inv-31: Lomitapide (Juxtapid) — Maximum 60 mg/day (capsule availability noted)

Maximum 60 mg/day (capsule availability)Maximum lomitapide dose is 60 mg/day; capsules are available in 5, 10, 20, and 30 mg strengths

Titration schedule summaryInitial 5 mg QD for ≥2 weeks, then 10/20/40 mg QD each for ≥4 weeks before escalation toward max as tolerated

Monitoring and adjustmentsEscalate based on tolerability; modify dose for CYP3A4 inhibitors, renal or hepatic impairment, and elevated transaminases

SAMS listed in Appendix A (abbreviation/acronym key) and discussed in Appendix G clinical descriptions

Use in criteriaSAMS is used to define statin intolerance pathways in initial therapy criteria

inv-21: Very high risk ASCVD — definition includes multiple major events or one major event plus multiple high-risk conditions.

Very high risk ASCVD definition (events/conditions)Very high risk is having either multiple major ASCVD events OR one major ASCVD event plus multiple high‑risk conditions (see Appendix H for lists)

Examples of major ASCVD eventsMajor events include recent acute coronary syndrome (within 12 months), prior MI, ischemic stroke, or symptomatic PAD

Examples of high‑risk conditionsHigh‑risk conditions include age ≥ 65, FH, prior CABG/PCI, diabetes, hypertension, CKD (eGFR 15–59), current smoking, persistently elevated LDL‑C despite therapy, and CHF

inv-22: SAMS description — muscle symptoms typical presentation and persistence note.

Typical presentation of SAMSMuscle pain and aching (myalgia), cramps, and weakness, usually bilateral and involving large muscle groups (thigh, buttock, back, shoulder girdle)

Timing and resolutionSymptoms often appear early after starting or increasing statin dose and usually resolve within weeks after stopping therapy, but may take months to fully resolve

Persistence notePersistence of symptoms >2 months after drug cessation should prompt evaluation for other causes or underlying muscle disease; reappearance with rechallenge supports SAMS diagnosis

Added requirement for adherence to statin therapy on re-authorization (1Q 2021 annual review).