Sodium Phenylbutyrate/Taurursodiol (AMX0035) Form

Sodium phenylbutyrate/taurursodiol (Relyvrio™) is coformulation of the compounds sodium phenylbutyrate, a molecular chaperone, and taurursodiol, a Bax inhibitor. FDA Approved Indication(s)
Relyvrio is indicated for the treatment of amyotrophic lateral sclerosis (ALS) in adults.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Relyvrio is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Amyotrophic Lateral Sclerosis (must meet all):

1. Diagnosis of definite ALS per revised El Escorial diagnostic criteria (see Appendix D);
2. Prescribed by or in consultation with a neurologist;
   
   3. Age ≥ 18 years;
   4. Concomitant use of riluzole (at up to maximally indicated doses), unless contraindicated or clinically significant adverse effects are experienced;
3. Percent predicted slow vital capacity (SVC) > 60%;
   6. Symptom onset of ≤ 18 months;
   7. Member does not have presence of tracheostomy or permanent assisted ventilation;
   8. Dose does not exceed 6 g sodium phenylbutyrate/2 g taurursodiol (2 packets) per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or Page 1 of 6

   CLINICAL POLICY Sodium Phenylbutyrate/Taurursodiol b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Amyotrophic Lateral Sclerosis (must meet all):
   
   1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
6. Member is responding positively to therapy (e.g., no tracheostomy or permanent assisted ventilation);
7. If request is for a dose increase, new dose does not exceed 6 g sodium phenylbutyrate/2 g taurursodiol (2 packets) per day. Approval duration: 6 months
   B. Other diagnoses/indications (must meet 1 or 2):
8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

9. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – Page 2 of 6

   CLINICAL POLICY Sodium Phenylbutyrate/Taurursodiol CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key ALS: amyotrophic lateral sclerosis EMG: electromyography FDA: Food and Drug Administration LMN: lower motor neuron SVC: slow vital capacity UMN: upper motor neuron disease Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen riluzole (Rilutek®) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. 50 mg PO BID Dose Limit/ Maximum Dose 100 mg/day Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Revised El Escorial diagnostic criteria for ALS requires the presence of:

10. Signs of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination,

11. Signs of upper motor neuron (UMN) degeneration by clinical examination, and

    3. Progressive spread of signs within a region or to other regions, together with the absence of: a. Electrophysiological evidence of other disease processes that might explain the signs of LMN and/or UMN degenerations; and b. Neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiological signs. • The definitions of ALS diagnoses provided by the revised El Escorial criteria are as follows: Clinically definite ALS Clinically probable ALS Clinically probable lab- supported ALS Clinically possible ALS Revised El Escorial criteria Clinical/electromyography (EMG) evidence of upper and lower motor neuron signs in ≥ 3 regions Clinical/EMG evidence of upper and lower motor neuron signs in ≥ 2 regions, with some upper motor neuron signs rostral to lower motor neuron signs Clinical upper and lower motor neuron signs in 1 region and lower motor neuron signs in 2 regions Clinical/EMG evidence of upper and lower motor neuron signs in 1 region OR Page 3 of 6

    CLINICAL POLICY Sodium Phenylbutyrate/Taurursodiol Revised El Escorial criteria Isolated upper motor neuron signs in ≥ 2 regions OR Lower motor neuron signs rostral to upper motor neuron signs Appendix E: Riluzole Co-administration There is support for the co-administration of riluzole in ALS: • The 2009 American Academy of Neurology ALS guideline for the care of the patient with ALS (reaffirmed January 2020) recommends that riluzole should be offered to slow disease progression (Level A).
    • The 2020 Canadian best practice recommendations for the management of ALS state the following: riluzole has demonstrated efficacy in improving survival in ALS (level A), there is evidence that riluzole prolongs survival by a median duration of 3 months (level A), and riluzole should be started soon after the diagnosis of ALS (expert consensus).
    • Additionally, approximately 71% of patients in the phase 2 CENTAUR trial were receiving concomitant riluzole. V. Dosage and Administration
    Indication Dosing Regimen ALS 1 packet (3 g sodium phenylbutyrate and 1 g taurursodiol) daily for the first 3 weeks, followed by 1 packet twice daily thereafter Maximum Dose 2 packets (6 g sodium phenylbutyrate and 2 g taurursodiol) per day VI. Product Availability
    Powder for oral suspension: 3 g of sodium phenylbutyrate and 1 g of taurursodiol in single dose packet VII.