CurrentAmbetter NevadaPolicy CP.PHAR.810

Clinical Policy: Oveporexton (Orzeyful)

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Prior authorization and medical-necessity coverage for oveporexton (Orzeyful), primarily for adults with narcolepsy type 1 with cataplexy, across commercial, health insurance marketplace/ICHRA, and Medicaid lines of business, subject to applicable benefit and state Medicaid provisions.

Policy Summary

PayerAmbetter Nevada

PolicyClinical Policy: Oveporexton (Orzeyful)

Policy CodePolicy CP.PHAR.810

Change TypeNo material change

Effective DateDecember 1, 2026

Last ReviewNov 1, 20265d

Next Review DateN/A

Key ActionSubmit clinical documentation demonstrating that all applicable approval criteria are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

4 mg/dayMaximum daily dose

2 tablets/dayMaximum tablets per day

12 monthsApproval duration

Adult narcolepsy type 1Covered indication

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CurrentAmbetter NevadaPolicy CP.PHAR.810

Clinical Policy: Oveporexton (Orzeyful)

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Policy Summary

PayerAmbetter Nevada

PolicyClinical Policy: Oveporexton (Orzeyful)

Policy CodePolicy CP.PHAR.810

Change TypeNo material change

Effective DateDecember 1, 2026

Last ReviewNov 1, 20265d

Next Review DateN/A

Key ActionSubmit clinical documentation demonstrating that all applicable approval criteria are met.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

4 mg/dayMaximum daily dose

2 tablets/dayMaximum tablets per day

12 monthsApproval duration

Adult narcolepsy type 1Covered indication

Coverage Criteria

Initial therapy - narcolepsy with cataplexy

Covered for initial therapy when all criteria are met.

Initial approval - narcolepsy with cataplexy

Core eligibility: Member has narcolepsy with cataplexy; the medication is prescribed by or in consultation with a neurologist or sleep medicine specialist; and the member is age 18 years or older.Age ≥ 18 years
Objective diagnostic confirmation
- MSLT pathway: Cataplexy associated with narcolepsy is confirmed by a documented multiple sleep latency test (MSLT) showing mean sleep latency of 8 minutes or less and evidence of 2 or more sleep-onset rapid eye movement periods (SOREMPs).Mean sleep latency ≤ 8 minutes; ≥ 2 SOREMPs
- MSLT and PSG pathway: Cataplexy associated with narcolepsy is confirmed by a documented MSLT showing at least 1 SOREMP and a SOREMP lasting less than 15 minutes on the preceding overnight polysomnography (PSG).≥ 1 MSLT SOREMP; PSG SOREMP < 15 minutes
- CSF pathway: Lumbar puncture shows a cerebrospinal fluid (CSF) hypocretin-1 level of 110 pg/mL or less.CSF hypocretin-1 ≤ 110 pg/mL
Step-therapy requirement: Member has failed 2 of the following agents, with each agent used for at least 1 month, unless the member is age 65 or older, experiences clinically significant adverse effects, or all applicable agents are contraindicated: venlafaxine, fluoxetine, atomoxetine, clomipramine, or protriptyline.Failure of 2 agents; each used ≥ 1 month
For members age 65 or older, tricyclic antidepressants are not required for trial. For Illinois HIM requests, the step-therapy requirement does not apply under Illinois HB 5395.
Dose limit: The requested dose does not exceed both 4 mg per day and 2 tablets per day.≤ 4 mg/day and ≤ 2 tablets/day

Other diagnoses or indications

Other diagnoses or indications must meet one of the applicable pathways.

Recent label change pathway: If the drug has undergone a label change within the last 6 months that is not yet reflected in this policy, refer to the applicable no-coverage or non-formulary policy based on formulary or preferred drug list status and line of business.Within the last 6 months
For formulary or preferred drug list products, use the applicable no-coverage criteria policy. For products not on the formulary or preferred drug list, use the applicable non-formulary policy.
Off-label pathway: If the requested use, such as the diagnosis, age, or dosing regimen, is not specifically listed under the diagnoses or indications for which coverage is not authorized, and the recent-label-change pathway does not apply, refer to the applicable off-label use policy for the relevant line of business.

Continuation therapy - narcolepsy with cataplexy

Covered for continued therapy when all criteria are met.

Continued therapy - narcolepsy with cataplexy

Eligibility for continuation: Member is currently receiving the medication through the Centene benefit or has previously met the initial approval criteria, or the member is currently receiving the medication and is enrolled in a state and product subject to continuity-of-care regulations.
Refer to the applicable state-specific continuity-of-care addendums, CC.PHARM.03A and CC.PHARM.03B.
Positive response: Member is responding positively to therapy, such as through a reduction in the frequency of cataplexy attacks.
Dose-increase limit: If the request is for a dose increase, the new dose does not exceed both 4 mg per day and 2 tablets per day.≤ 4 mg/day and ≤ 2 tablets/day
Applies only when a dose increase is requested.

Non-FDA-approved indications that are not addressed in this policy are not authorized for coverage unless sufficient documentation of efficacy and safety is provided under the applicable off-label use policy or evidence of coverage documents.

Clinical Thresholds and Dose Parameters

Coding

Mean sleep latency≤ 8 minutes

Coding

MSLT findingEvidence of 2 or more SOREMPs

Coding

Overnight PSG findingAt least 1 SOREMP, less than 15 minutes, on the preceding overnight PSG

Coding

CSF hypocretin-1 level

Prior Authorization and Documentation

Prior Authorization

Initial Prior Authorization

Submit an initial prior authorization request with documentation supporting that the member meets all applicable initial approval criteria. When approved, coverage is authorized for 12 months, subject to the policy limits.

Orzeyful (oveporexton) is reviewed under the initial approval criteria for narcolepsy with cataplexy.
Approved dose may not exceed 4 mg per day and 2 tablets per day.

Prior Authorization

Renewal Prior Authorization

Submit a renewal prior authorization request before the 12-month approval period ends. Continued coverage requires evidence of eligibility for continuation and a positive response to therapy.

The member must be receiving the medication through a Centene benefit, have previously met initial approval criteria, or qualify under applicable continuity-of-care regulations.
For a dose increase, the new dose may not exceed 4 mg per day or 2 tablets per day.

Drug and Indication Background

Oveporexton (Orzeyful) is an orexin receptor 2 agonist. This policy addresses the FDA-approved treatment of narcolepsy type 1, also described as narcolepsy with cataplexy, in adults. Diagnostic support may include multiple sleep latency testing with sleep-onset rapid eye movement periods or a cerebrospinal fluid hypocretin-1 level of ≤ 110 pg/mL.

Definitions and Abbreviations

Definitions

OveporextonAn orexin receptor 2 agonist.

Definitions

CSFCerebrospinal fluid.

Definitions

FDAFood and Drug Administration.

Definitions

MSLTMultiple sleep latency test.

Initial Therapy Criteria

Initial therapy - narcolepsy with cataplexy

Initial therapy for narcolepsy with cataplexy requires all listed criteria.

Core eligibility: Member has narcolepsy with cataplexy; the medication is prescribed by or in consultation with a neurologist or sleep medicine specialist; and the member is age 18 years or older.Age ≥ 18 years
Objective diagnostic confirmation
- MSLT pathway: Cataplexy associated with narcolepsy is confirmed by a documented MSLT showing mean sleep latency of 8 minutes or less and evidence of 2 or more SOREMPs.Mean sleep latency ≤ 8 minutes; ≥ 2 SOREMPs

Continuation Therapy Criteria

Continued therapy - narcolepsy with cataplexy

Continued therapy for narcolepsy with cataplexy requires all listed criteria.

Eligibility for continuation: Member qualifies through current therapy under the Centene benefit, prior satisfaction of the initial approval criteria, or applicable continuity-of-care regulations.
For continuity-of-care eligibility, refer to the applicable state-specific continuity-of-care addendums, CC.PHARM.03A and CC.PHARM.03B.
Positive response: Member is responding positively to therapy, such as through a reduction in the frequency of cataplexy attacks.
Dose-increase limit: If the request is for a dose increase, the new dose does not exceed both 4 mg per day and 2 tablets per day.≤ 4 mg/day and ≤ 2 tablets/day

Step-Therapy Requirements

Step	Requirement	Alternative agents	Exceptions
1	Member must fail 2 agents, with each agent used for at least 1 month.	Venlafaxine; fluoxetine; atomoxetine; clomipramine; or protriptyline.	The requirement does not apply if the member is age 65 or older, experiences clinically significant adverse effects, or all applicable agents are contraindicated. Tricyclic antidepressants are not required for trial when the member is age 65 or older. For Illinois HIM requests, step therapy does not apply under Illinois HB 5395.

Quantity and Dose Limits

Quantity Limits

Maximum daily quantity4 mg per day

Quantity Limits

Maximum daily tablet quantity2 tablets per day

Policy Summary

PayerAmbetter Nevada

PolicyClinical Policy: Oveporexton (Orzeyful)

Policy CodePolicy CP.PHAR.810

Change TypeNo material change

Effective DateDecember 1, 2026

Last ReviewNov 1, 20265d

Next Review DateN/A

Key ActionSubmit clinical documentation demonstrating that all applicable approval criteria are met.

SourceLink

On This Page

Coding

Alternative-agent trialFailure of 2 agents, with each failed agent used for ≥ 1 month

Coding

Maximum daily dose≤ 4 mg/day

Maximum tablets per day≤ 2 tablets/day

Step Therapy

Failure of Two Alternative Agents

Document failure of two required alternative agents before requesting initial approval, unless an applicable exception applies.

Trial two of the following agents, with each used for at least 1 month: venlafaxine, fluoxetine, atomoxetine, clomipramine, or protriptyline.
The trial requirement does not apply when the member is age 65 years or older, has clinically significant adverse effects, or all applicable alternatives are contraindicated.
For members age 65 or older, tricyclic antidepressants are not required for the trial.

Step Therapy

Illinois HIM Step-Therapy Exception

For Illinois HIM requests, do not apply the step-therapy requirements described in the initial criteria.

The Illinois exception applies under IL HB 5395.
The exception removes the requirement to fail two alternative agents.

Documentation Required

Clinical Documentation Required

Provider must submit documentation supporting that the member has met all approval criteria. Supporting material may include office chart notes, laboratory results, and other relevant clinical information.

Include records sufficient to substantiate the diagnosis, specialist involvement, age, diagnostic findings, alternative-agent history or applicable exception, dose, response to therapy, and continuity-of-care eligibility when relevant.

Documentation Required

Evidence for Initial Approval

For an initial request, document all of the following: narcolepsy with cataplexy; prescribing by or consultation with a neurologist or sleep medicine specialist; age 18 years or older; and qualifying objective evidence of cataplexy associated with narcolepsy.

Document a multiple sleep latency test (MSLT) showing mean sleep latency ≤ 8 minutes with evidence of at least two SOREMPs; or one SOREMP on MSLT plus a SOREMP of less than 15 minutes on the preceding overnight polysomnography (PSG).
Alternatively, document lumbar puncture results showing cerebrospinal fluid hypocretin-1 level ≤ 110 pg/mL.

Documentation Required

Evidence for Continuation

For continued therapy, document that the member qualifies for continuation and is responding positively to Orzeyful.

Acceptable continuation eligibility includes current receipt through a Centene benefit, previous satisfaction of initial approval criteria, or current therapy under applicable state and product continuity-of-care regulations.
Document positive response, such as a reduction in the frequency of cataplexy attacks.
If requesting a dose increase, document that the new dose is within the policy maximums.

Denial Risk

Unaddressed Non-FDA-Approved Indication

Coverage is not authorized for non-FDA-approved indications that are not addressed by this policy.

An exception may apply when sufficient documentation of efficacy and safety supports the off-label use under the applicable policy: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, or CP.PMN.53 for Medicaid, or under evidence-of-coverage documents.

Denial Risk

Failure to Meet Initial Criteria

An initial request may be denied when the member does not satisfy every applicable initial approval requirement.

The request must establish narcolepsy with cataplexy, specialist prescribing or consultation, age 18 years or older, and qualifying diagnostic evidence.
The request must also satisfy the alternative-agent requirement or a stated exception, and remain within the dose limits of 4 mg per day and 2 tablets per day.

Denial Risk

Failure to Meet Continuation Criteria

A continued-therapy request may be denied when the member does not satisfy every applicable continuation requirement.

The request must establish qualifying prior or current therapy eligibility and a positive response to treatment.
A requested dose increase must remain within 4 mg per day and 2 tablets per day.

Definitions

SOREMPSleep-onset rapid eye movement period.

Definitions

PSGPolysomnography.

MSLT and PSG pathway: Cataplexy associated with narcolepsy is confirmed by a documented MSLT showing at least 1 SOREMP and a SOREMP lasting less than 15 minutes on the preceding overnight PSG.≥ 1 MSLT SOREMP; PSG SOREMP < 15 minutes

CSF pathway: Lumbar puncture shows a CSF hypocretin-1 level of 110 pg/mL or less.CSF hypocretin-1 ≤ 110 pg/mL

Step-therapy requirement: Member has failed 2 of the following agents, with each agent used for at least 1 month, unless the member is age 65 or older, experiences clinically significant adverse effects, or all applicable agents are contraindicated: venlafaxine, fluoxetine, atomoxetine, clomipramine, or protriptyline.Failure of 2 agents; each used ≥ 1 month

For members age 65 or older, tricyclic antidepressants are not required for trial. For Illinois HIM requests, the step-therapy requirement does not apply under Illinois HB 5395.

Dose limit: The requested dose does not exceed both 4 mg per day and 2 tablets per day.≤ 4 mg/day and ≤ 2 tablets/day

Applies only when a dose increase is requested.