ModifiedmhnPolicy CP.PHAR.584

Sodium phenylbutyrate/taurursodiol (Relyvrio) policy

Defines medical necessity, authorization, and continuation criteria for Relyvrio for adults with ALS and references handling of other indications and market withdrawal; applies to Centene-affiliated health plans and specified lines of business.

Policy Summary

Payermhn

PolicySodium phenylbutyrate/taurursodiol (Relyvrio) policy

Policy CodePolicy CP.PHAR.584

Change TypeMaterial revision — limited continuationinitial starts prohibited

Effective DateSep 29, 2022

Next Review DateN/A

Key ActionSubmit prior authorization only for current Relyvrio users; approvals are limited to a one-month authorization to allow transition to manufacturer programs.

SourceLink

POLICY UPDATE CHANGES

Initial approval criteria were removed and continued authorization was limited to 1 month due to manufacturer withdrawal of Relyvrio from the market.

ICHRA line of business was added to the policy coverage lines.

Added ICHRA line of business.

Removed initial approval criteria and limited continued authorization to 1 month due to manufacturer withdrawal.

Updated criteria per FDA labeling to add maximum dose of 2 packets/day and examples of positive response (no tracheostomy or permanent assisted ventilation).

Updated Appendix D table of revised El Escorial criteria.

1 monthmax continuation duration

2 packets/daymax daily dose

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new starts prohibited after

Adults with ALSFDA approved indication

ICHRAline of business added

Coverage Criteria for Relyvrio (sodium phenylbutyrate/taurursodiol)

Continuation Therapy (current users only)

Covered when ALL of the following are met for continuation in current users:

ALS continuation eligibility: Member meets one of the following: (a) currently receiving medication via Centene benefit or has previously met initial approval criteria; OR (b) member is currently receiving medication and is enrolled in a state/product with continuity of care regulations

(criterion A.1)

Positive clinical response: Member is responding positively to therapy (examples include no tracheostomy or permanent assisted ventilation)

(criterion A.2)

Transition/authorization duration: If the member wishes to continue using Relyvrio, authorization is limited to up to 1 month to allow transition to the manufacturer's free drug program<= 1 month

(criterion A.3)

Dose limit: Requested dose (including any dose increase) does not exceed 6 g sodium phenylbutyrate / 2 g taurursodiol (2 packets) per day<= 2 packets/day

(criterion A.4)

Initial Therapy

Not authorized for new initiation:

New starts prohibited: Authorization for initiation of Relyvrio is not permitted; members may not initiate therapy due to the manufacturer's voluntary market withdrawal effective April 4, 2024

Approval duration: Not applicable

Coverage constraints and authorization limits

Policy criteria updated per FDA labeling and manufacturer status; continued authorization parameters altered.

Updated coverage constraints: Dosing must not exceed 2 packets/day (6 g sodium phenylbutyrate / 2 g taurursodiol); continued authorization is limited to 1 month due to manufacturer withdrawal; examples of positive clinical response include no tracheostomy or permanent assisted ventilation2 packets/day; continued auth <= 1 month

Full initial approval criteria were removed following market withdrawal; providers must document clinical response and dosing

Coverage for non‑FDA approved indications of sodium phenylbutyrate/taurursodiol (Relyvrio) is not authorized under this policy unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies. See commercial policy CP.CPA.09, ICHRA policy HIM.PA.154, or Medicaid policy CP.PMN.53 (or other evidence‑of‑coverage documents) for the required supporting information and review standards.

The policy’s initial approval criteria were removed following the manufacturer’s market withdrawal. Operationally, this means prior language authorizing new starts under those former initial criteria is no longer present in the policy; continued access has been limited and the policy now focuses on continuation for current users and transition planning.

Initiation of Relyvrio for patients who were not already receiving the drug is not authorized. The manufacturer voluntarily discontinued marketing and removed Relyvrio from the market, and the product is unavailable for new patients as of April 4, 2024; prescribers should not initiate new treatment effective that date.

Removal of the initial approval criteria combined with the manufacturer withdrawal has operational consequences: prior authorizations for continuation are now constrained to support only members already on therapy, and continued authorization has been shortened to a maximum of 1 month to allow transition to manufacturer free‑drug programs. Requests that do not meet the updated continuation criteria or dosing limits may be denied.

Product and Billing Codes / Dose Limits

Product codesmixed

NDC	Not listed in this document

Affected Codes (unspecified in these chunks)mixed

affected codes

placeholder reference to codes impacted by prior authorization changes

inv-10: Maximum daily dose — 2 packets/day (6 g sodium phenylbutyrate / 2 g taurursodiol)

Maximum daily dose2 packets per day = 6 g sodium phenylbutyrate / 2 g taurursodiol

Packet composition1 packet = 3 g sodium phenylbutyrate + 1 g taurursodiol

Typical titrationInitial: 1 packet daily for first 3 weeks, then 1 packet twice daily thereafter

inv-11: Maximum daily dose — 2 packets/day (alternate reference)

Maximum daily dose (alternate reference)2 packets per day

Policy labeling updateFDA labeling and policy updated to add maximum dose of 2 packets/day

Prior Authorization, Documentation, and Provider Responsibilities

Prior Authorization

Prior authorization: continuation only, limited to 1 month

Prior authorization for continued Relyvrio may be approved only for members who are already receiving the medication through the Centene benefit or who previously met initial approval criteria; authorization for continuation is limited to a one-month approval to allow transition to the manufacturer's free drug program.

Member must be currently receiving medication via Centene benefit or have previously met initial approval criteria.
Approval duration for continued therapy: 1 month to allow transition to manufacturer free-drug program.

Prior Authorization

Prior authorization changes after market withdrawal

The policy removed initial approval criteria and now limits any continued authorization to a single one-month approval following the manufacturer's voluntary market withdrawal; dosing was also aligned with FDA labeling (maximum 2 packets/day).

Initial approval criteria removed after manufacturer withdrawal.
Continued authorization limited to 1 month.

Background and Scope

Relyvrio is a coformulation of sodium phenylbutyrate and taurursodiol indicated for the treatment of adults with amyotrophic lateral sclerosis (ALS). The manufacturer voluntarily discontinued marketing after topline results from the phase 3 PHOENIX trial failed to meet the primary endpoint; as a result, the product was removed from the U.S. market and is unavailable for new patients as of April 4, 2024. Providers should note the product formulation and the current availability status when assessing therapy options and documenting transition plans.

Definitions and Diagnostic Criteria

inv-21: Relyvrio — Coformulation of sodium phenylbutyrate and taurursodiol

Product identityRelyvrio is a coformulation of sodium phenylbutyrate and taurursodiol

Sodium phenylbutyrate roleActs as a molecular chaperone (per product description)

Taurursodiol roleFunctions as a Bax inhibitor (per product description)

inv-22: Revised El Escorial criteria — Diagnostic criteria for ALS (clinical and electrophysiological UMN/LMN evidence and spread)

Required elementsRevised El Escorial criteria require LMN degeneration (clinical, electrophysiologic or neuropathologic), UMN degeneration (clinical), and progressive spread of symptoms or signs

Exclusion requirementsAbsence of electrophysiological or neuroimaging evidence of other disease processes that could explain LMN/UMN signs

Policy Summary

Payermhn

PolicySodium phenylbutyrate/taurursodiol (Relyvrio) policy

Policy CodePolicy CP.PHAR.584

Change TypeMaterial revision — limited continuationinitial starts prohibited

Effective DateSep 29, 2022

Next Review DateN/A

Key ActionSubmit prior authorization only for current Relyvrio users; approvals are limited to a one-month authorization to allow transition to manufacturer programs.

SourceLink

On This Page

Dose equivalence2 packets = 6 g sodium phenylbutyrate and 2 g taurursodiol

Dosing aligned to maximum of 2 packets/day per FDA labeling.

Note

Therapeutic alternatives and formulary PA

Therapeutic alternatives such as riluzole are listed in Appendix B and may require prior authorization per the formulary and the member’s line of business.

Appendix B lists riluzole (Rilutek) 50 mg PO BID, maximum 100 mg/day as an alternative.
Alternative agents may not be formulary for all lines of business and may require PA.

Step Therapy

Step therapy: none stated

No step therapy requirements are specified in the policy; the document states that no explicit step therapy requirements are present in these sections.

Policy does not establish any step edits or required trials prior to continuation or alternatives.

Documentation Required

Required documentation for PA

Providers must submit supporting clinical documentation—such as office chart notes, laboratory results, or other clinical information—demonstrating that the member meets all applicable approval criteria.

Include recent office notes documenting ongoing Relyvrio use and clinical response.
Attach relevant lab results or other objective clinical data that support continued therapy.

Documentation Required

Documentation expectations: dosing and response

Document the member’s dosing (not to exceed 2 packets per day) and note policy changes and FDA labeling updates; providers should also document response status (examples include no tracheostomy or permanent assisted ventilation).

Record current daily dose and ensure requested dose does not exceed 6 g sodium phenylbutyrate/2 g taurursodiol (2 packets/day).
Document positive response examples, e.g., absence of tracheostomy or permanent assisted ventilation.
Reference Appendix F (withdrawal notice) and any relevant FDA labeling revisions when submitting PA.

Denial Risk

New starts prohibited (effective April 4, 2024)

Requests to initiate Relyvrio for new patients will be denied; physicians should not start new patients on Relyvrio effective April 4, 2024, due to the manufacturer’s voluntary market withdrawal.

New patient initiation is not authorized and approval duration for initiation is not applicable.
Action required for prescribers: do not initiate new treatment effective April 4, 2024.

Denial Risk

Denial risks from withdrawal and labeling changes

Because the manufacturer voluntarily withdrew Relyvrio from the U.S. market, continued authorization is limited to one month; failure to meet updated criteria (including the maximum 2 packets/day dosing and evidence of positive response) may result in denial.

Continued authorization limited to 1 month to permit transition to manufacturer free-drug program.
Denial risk if dosing exceeds 2 packets/day or if required documentation of positive response is not provided.

Diagnostic categoriesDefines clinically definite, probable, probable lab-supported, and possible ALS based on regional UMN/LMN findings

inv-23: Examples of positive response — No tracheostomy or permanent assisted ventilation cited as examples of a positive response to therapy.

Examples of positive responseNo tracheostomy or permanent assisted ventilation cited as examples of a positive response to therapy

Use in continuation decisionsPolicy uses positive response (examples above) as part of continuation eligibility following manufacturer withdrawal

Documentation expectationProviders should document response status when requesting continued authorization