ModifiedCentenePolicy CP PHAR.584

Sodium Phenylbutyrate/Taurursodiol (Relyvrio) coverage

Coverage policy for Relyvrio for treatment of amyotrophic lateral sclerosis (ALS) for Centene lines of business (Commercial, HIM, Medicaid). Specifies initial and continued therapy criteria, documentation requirements, and market withdrawal guidance.

Policy Summary

PayerCentene

PolicySodium Phenylbutyrate/Taurursodiol (Relyvrio) coverage

Policy CodePolicy CP PHAR.584

Change TypeManufacturer market withdrawal — initiation prohibitedcontinuation limited

Effective DateSep 29, 2022

Next Review DateN/A

Key ActionDo not initiate Relyvrio for new patients; prior authorization for new starts will be denied and continuation authorizations are limited to one month with transition options to manufacturer programs for existing patients.

SourceLink

POLICY UPDATE CHANGES

Manufacturer voluntarily discontinued marketing authorization and Relyvrio is no longer available for new patients as of April 4, 2024.

Initial authorization for Relyvrio is not permitted (no new starts).

Removed initial approval criteria and limited continued authorization to 1 month due to manufacturer withdrawal; added Appendix F with details of market withdrawal.

Added maximum dose of 2 packets/day consistent with FDA labeling.

Apr 4, 2024market withdrawal date

AdultsFDA-approved population

2 packets/day

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Commercial, HIM, Medicaidlines of business

1 monthcontinued auth limit

Coverage Criteria

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

Covered when ALL of the following are met

Initial Approval: Authorization is not permitted; member may not initiate therapy with Relyvrio because the manufacturer voluntarily discontinued marketing authorization and Relyvrio is no longer available for new patients as of April 4, 2024.

See Appendix F for manufacturer program for existing patients

inv-02: Continuation/Renewal — Covered when ALL of the following are met

Covered when ALL of the following are met

Continued Therapy - ALS: Member is currently receiving medication via the Centene benefit or has previously met initial approval criteria; member is responding positively to therapy (for example, no tracheostomy or permanent assisted ventilation).

If member wishes to continue, transition to manufacturer free drug program may be arranged per Appendix F; approval duration: 1 month; maintenance dosing consistent with 2 packets/day.

inv-03: Continuation Therapy (restricted due to withdrawal) — Policy changes governing authorization after manufacturer withdrawal

Policy changes governing authorization after manufacturer withdrawal

Continued authorization limited: Continued authorization for members already receiving therapy is limited to 1 month following manufacturer withdrawal.1 month

Initial approval criteria were removed; see Appendix F for market withdrawal details and instructions for transition to a free drug program.

Non-FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety consistent with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid).

The policy was updated to reflect the manufacturer's market withdrawal: initial approval criteria for starting Relyvrio were removed and continued authorization rules were revised. See policy history for the change dated 04.04.24 noting removal of initial approval criteria and limitation of continued authorization to one month.

Initiation of Relyvrio for new patients is not authorized. The manufacturer voluntarily discontinued marketing authorization and Relyvrio was removed from the market; the product was no longer available for new patients as of April 4, 2024. Providers should not start new treatment with Relyvrio and should refer to Appendix F for transition options for existing patients.

The provided document sections do not list specific clinical conditions that are designated as ‘not medically necessary’ beyond the operational restriction on initiation. Operational changes removed initial approval criteria after the manufacturer withdrawal and limited continued authorization to 1 month, thereby effectively restricting initiation of therapy for any new clinical presentation.

Initial Therapy Criteria

inv-23: Initial Therapy — initial therapy initiation restriction

Covered when ALL of the following are met

Initial therapy: Authorization for initiation is not permitted because the manufacturer discontinued marketing authorization; Relyvrio is not available for new patients as of April 4, 2024.

See Appendix F for transition program for existing patients.

inv-24: Initial therapy — initial approval changes

Covered when ALL of the following are met

Initial therapy removed: Initial approval criteria were removed following manufacturer market withdrawal; initiation guidance is not provided in this policy.

See Appendix F and policy history for details.

Continuation Therapy Criteria

inv-25: Continuation Therapy — continuation allowed for patients already receiving therapy

Covered when ALL of the following are met

Continuation: Member is currently receiving Relyvrio or previously met initial criteria; member is responding positively to therapy (for example, no tracheostomy or permanent assisted ventilation).

Transition to manufacturer free drug program available per prescriber and manufacturer instructions; approval duration: 1 month; maintenance dose: 2 packets/day.

inv-26: Continuation therapy — continuation rules updated after manufacturer withdrawal

Covered when ALL of the following are met

Max dose and limited continuation: Continued therapy may be authorized for a limited period (1 month) and maximum dosing per FDA labeling is 2 packets per day.2 packets/day

Policy removed initial approval criteria; continuation limited due to market withdrawal.

Coding

References (no explicit billing codes provided)mixed

No codes listed

Maintenance dosing — Relyvrio (sodium phenylbutyrate/taurursodiol)

Maintenance dosing2 packets per day (total daily: 6 g sodium phenylbutyrate and 2 g taurursodiol)

Titration schedule (label)1 packet once daily for first 3 weeks, then 1 packet twice daily thereafter (per prescribing information)

Packet contentEach single‑dose packet contains 3 g sodium phenylbutyrate and 1 g taurursodiol

Provider Actions & Operational Notes

Prior Authorization

Prior authorization / New starts prohibited

Prior authorization is required; however, initial authorization (new starts) is not permitted because the manufacturer voluntarily discontinued marketing authorization and removed Relyvrio from the U.S. market effective April 4, 2024. Requests for initiation of therapy will be denied.

New starts prohibited as of April 4, 2024 (Appendix F)

Prior Authorization

Prior authorization and dosing limits

Continued therapy may be considered only for current patients and is subject to dosing limits and shortened authorization periods due to the market withdrawal. Initial approval was removed and continued authorization has been limited to one month.

Continued authorization limited to 1 month
Maximum dosing per prior FDA label (see policy dosing section) may apply for continuation

Step Therapy / Alternative Coverage Pathways

Step	Requirement / Routing
1	For requested uses or formulations not specifically covered in this policy, refer to the applicable formulary/no-coverage policy or the off-label use policy for the member's line of business (e.g., CP.CPA.190, HIM.PA.33, CP PMN.255; off‑label policies CPCPA.09, HIMPA.154, CP.PMN.53).

Step	Requirement
1	No step therapy requirements are specified in the provided sections of this policy.

Definitions

Revised El Escorial criteria — diagnostic summary

DefinitionRevised El Escorial criteria: clinical and electrophysiological criteria defining upper motor neuron (UMN) and lower motor neuron (LMN) signs across regions to classify ALS (definite, probable, possible).

Required elementsPresence of LMN signs, presence of UMN signs, progressive spread of signs between regions, and exclusion of other explanatory disease processes (clinical, electrophysiologic, neuroimaging).

Category examplesClinically definite ALS = UMN and LMN signs in ≥3 regions; Clinically probable ALS = UMN and LMN signs in ≥2 regions (with variants noted by lab support); Clinically possible ALS = isolated presentations per criteria.

Riluzole co-administration — clinical guidance

Guideline recommendationRiluzole should be offered to slow disease progression (American Academy of Neurology guideline, reaffirmed 2023).

Background

Relyvrio (sodium phenylbutyrate/taurursodiol) is a coformulation indicated for treatment of amyotrophic lateral sclerosis (ALS) in adults. The policy references diagnostic guidance including the Revised El Escorial criteria for ALS and cites FDA prescribing information and clinical trial reports in its reference list.

Quantity Limits

Relyvrio (sodium phenylbutyrate/taurursodiol) — product summary

ProductRelyvrio (sodium phenylbutyrate/taurursodiol) — oral powder for suspension supplied in single‑dose packets.

Usual maintenance quantityDosing regimen per label leads to a maximum of 2 packets per day (total daily dose: 6 g sodium phenylbutyrate / 2 g taurursodiol).

Packet compositionEach packet contains 3 g sodium phenylbutyrate and 1 g taurursodiol (powder for oral suspension).

sodium phenylbutyrate/taurursodiol packet — product details

Unit descriptionSingle‑dose packet: powder for oral suspension containing 3 g sodium phenylbutyrate and 1 g taurursodiol.

Maximum packets/dayMaximum recommended dosing per FDA labeling: 2 packets per day (total daily: 6 g sodium phenylbutyrate and 2 g taurursodiol).

Site of Care

Note

No infusion center/site‑of‑care restrictions stated

No site‑of‑care restrictions or infusion center limitations are specified in the provided policy sections.

Revision History

2024-04-04manufacturer_withdrawal

Manufacturer voluntarily discontinued marketing authorization; initial authorization for Relyvrio is no longer permitted and prescribers should not initiate new treatment.

2024-04-04policy_revision

Removed initial approval criteria and limited continued authorization for members already receiving therapy to a one-month approval period due to manufacturer withdrawal; Appendix F added with market withdrawal details.

2022-10-06label_update

Policy updated to add maximum dose of 2 packets/day per FDA labeling and examples of positive response (e.g., no tracheostomy or permanent assisted ventilation); references reviewed and updated.

Policy Summary

PayerCentene

PolicySodium Phenylbutyrate/Taurursodiol (Relyvrio) coverage

Policy CodePolicy CP PHAR.584

Change TypeManufacturer market withdrawal — initiation prohibitedcontinuation limited

Effective DateSep 29, 2022

Next Review DateN/A

SourceLink

On This Page

Denial Risk

Denial risk following market withdrawal

Continued authorization carries increased risk of denial because of the manufacturer withdrawal and the policy limitation to a one-month continuation approval; providers should plan for potential denials and transition planning.

Denial risk elevated following April 4, 2024 market withdrawal
Authorization may be limited or denied at renewal beyond the one-month continuation

Documentation Required

Required documentation

Provider must submit supporting documentation (e.g., office chart notes, lab results, other clinical information) demonstrating that the member meets all applicable criteria for continued therapy.

Submit office chart notes, labs, and other clinical information to support continued use

Note

Documentation of policy changes and market withdrawal

Policy history documents the removal of initial approval and the limitation of continued authorization to one month due to the manufacturer's withdrawal; Appendix F (Withdrawal of Relyvrio from the US Market) summarizes the manufacturer announcement and effective date.

Policy history: initial approval removed; continued authorization limited to one month (04.04.24)
See Appendix F for full withdrawal details

Note

Formulary and off-label routing

For requests involving indications or formulary status not specifically addressed, follow the applicable formulary/no-coverage and off‑label policies for the member's line of business (commercial, marketplace, Medicaid) as referenced in this policy.

Commercial no-coverage/non-formulary: CP.CPA.190
Marketplace no-coverage/non-formulary: HIM.PA.33 / HIM.PA.103
Medicaid no-coverage/non-formulary: CP PMN.255 / CP PMN.16
Off-label policies: CPCPA.09 (commercial), HIMPA.154 (marketplace), CP.PMN.53 (Medicaid)

Effect on survivalRiluzole has demonstrated efficacy in improving survival in ALS, with evidence of a median survival prolongation (~3 months) per cited guidance.

Co-administration frequency in trialsApproximately 71% of participants in the phase 2 CENTAUR trial received concomitant riluzole, supporting co-administration with sodium phenylbutyrate/taurursodiol.

CENTAUR — trial reference

Trial nameCENTAUR (phase 2 randomized trial of sodium phenylbutyrate–taurursodiol in ALS)

Key publicationsPaganoni S, Macklin EA, Hendrix S, et al. Trial of sodium phenylbutyrate–taurursodiol for amyotrophic lateral sclerosis. N Engl J Med. 2020; and long‑term survival report (Muscle Nerve 2021).

Referenced in policyCENTAUR trial results are cited in the policy references and prescribing information for Relyvrio.

El Escorial criteria — policy definition

TermEl Escorial criteria (Revised): diagnostic framework for ALS based on UMN and LMN signs across regions, electrophysiology, progression, and exclusion of other causes.

Policy usageAppendix D contains the revised El Escorial criteria table; policy updates note Appendix D was updated during reviews.

Clinical categoriesDefines clinically definite, probable, probable lab‑supported, and possible ALS based on region involvement and EMG support.

Administration formPowder for oral suspension provided in single‑dose packets; initial dosing schedule per label includes a one‑packet once‑daily lead‑in then twice‑daily dosing.

2025-02-20annual_reviewLatest

2Q 2025 annual review: no significant clinical changes; references reviewed and updated and policy retained.