ModifiedCentenePolicy CP PHAR.432

Clinical Policy: Tafamidis (Vyndaqel, Vyndamax)

Defines medical necessity criteria and prior authorization requirements for tafamidis (Vyndaqel, Vyndamax) for treating wild-type or hereditary transthyretin-mediated cardiomyopathy (ATTR-CM) in adults for Centene lines of business.

Policy Summary

PayerCentene

PolicyClinical Policy: Tafamidis (Vyndaqel, Vyndamax)

Policy CodePolicy CP PHAR.432

Change TypeMaterial updates to concurrent-use exclusions and requirementsadded Attruby exclusion and conditional Amvuttra use

Effective DateSep 1, 2019

Next Review Date

Key ActionSubmit provider documentation (office notes, labs, imaging) showing member meets all approval criteria, including diagnostic confirmation and prior therapy response when requesting concurrent use.

SourceLink

POLICY UPDATE CHANGES

Added requirement that Vyndaqel/Vyndamax is not prescribed concurrently with Onpattro and Tegsedi (later revised to other agents) and updated contraindicated concurrent-use list over time.

Added requirements per pivotal trial inclusion criteria that member has NYHA Class I-III heart failure and at least 1 heart failure hospitalization or current clinical evidence of heart failure.

Removed Tegsedi from concurrent-use exclusion and later removed Amvuttra from the excluded list while adding specific requirements for concurrent use with Amvuttra.

Updated Appendix D removing Tegsedi and adding Amvuttra supplemental information on concurrent use; references reviewed and updated.

Added Attruby to the list of excluded agents for concurrent use in initial and continued therapy criteria.

Removed Amvuttra from list of excluded agents for concurrent use per HELIOS-B study and added requirements for concurrent use requests requiring positive but inadequate response to monotherapy.

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Coverage Criteria for Tafamidis (Vyndaqel, Vyndamax)

Initial Therapy

Covered when ALL of the following are met:

Initial Approval: Member has a diagnosis of ATTR-CM; prescribed by or in consultation with a cardiologist; age >= 18 years; diagnosis supported by either (A) tissue biopsy with transthyretin identified by mass spectrometry or immunohistochemistry (endomyocardial biopsy OR extracardiac biopsy with cardiac imaging [Echo, CMR, or PET] consistent with cardiac amyloidosis) OR (B) non-biopsy pathway with cardiac imaging consistent with amyloidosis plus Grade 2 or 3 cardiac uptake on a radionuclide scan using 99mTc-PYP, 99mTc-DPD, or 99mTc-HMDP, AND negative monoclonal protein testing (serum free light chains, serum and urine protein immunofixation); member has New York Heart Association (NYHA) Class I, II, or III heart failure AND either at least one hospitalization for heart failure prior or current (within the last 30 days) clinical evidence of heart failure (signs/symptoms per Appendix D); member has not had a liver transplant; dose does not exceed Vyndaqel 80 mg/day or Vyndamax 61 mg/day; Vyndaqel/Vyndamax is not prescribed concurrently with excluded agents unless concurrent-use conditions are met (see concurrent-use rules for Amvuttra and excluded agents such as Attruby/Onpattro).

Continuation Therapy

Covered for continuation when ALL of the following are met:

Continuation Approval: Member is currently receiving tafamidis through the Centene benefit or has previously met initial approval criteria; member is responding positively to therapy (improvement or stabilization in measures such as walking ability, nutrition/BMI, reduced cardiac-related hospitalizations, cardiac procedures or laboratory tests including echo, ECG, BNP/NT-proBNP, or troponin); tafamidis is not prescribed concurrently with excluded agents (e.g., Attruby or Onpattro) unless concurrent-use conditions are satisfied; dose does not exceed Vyndaqel 80 mg/day or Vyndamax 61 mg/day.

Concurrent Use, Exclusions, and Conditions

Coverage of tafamidis includes restrictions on concurrent use with certain agents; some agents are explicitly excluded while others (e.g., Amvuttra) may be allowed with conditions.

Concurrent use policy: ALL of the following must be met for concurrent therapy with other transthyretin-targeted agents: (1) the agent is not on the excluded list (Attruby has been added to the list of excluded agents; Onpattro is excluded) OR (2) if the agent (e.g., Amvuttra) was removed from the excluded list, the provider submits documentation of prior positive but inadequate response to monotherapy with that agent (e.g., maintained positive response after >= 6 months of monotherapy AND continued need such as ongoing cardiac-related hospitalizations despite monotherapy).

Reflects Appendix D updates and HELIOS-B evidence; concurrent-use requests for Amvuttra require documentation of prior positive but inadequate response to monotherapy; concurrent use with excluded agents (e.g., Attruby) is not permitted.

Coverage does not extend to non‑FDA approved indications for tafamidis unless the provider supplies sufficient clinical documentation meeting the applicable off‑label use policies (see CP.CPA.09, HIM.PA.154, CP.PMN.53). Requests for indications outside the FDA‑labeled ATTR‑CM indication that lack this documentation are not authorized and may be denied.

This policy’s coverage criteria also interact with the concurrent‑use rules in Appendix D: tafamidis must not be prescribed concurrently with agents that appear on the policy’s excluded list, and requests that would combine tafamidis with other transthyretin‑directed therapies must meet the specific concurrent‑use conditions described in the policy (for example, documentation requirements for agents removed from the excluded list).

Per the most recent Appendix D updates, Attruby has been added to the list of agents that are excluded from concurrent use with tafamidis for both initial approval and continued therapy; prescriptions that propose combination use with Attruby are not permitted under the concurrent‑use rules.

Use of tafamidis for non‑FDA indications is not covered unless the request includes sufficient documentation of efficacy and safety in accordance with the applicable off‑label policies (CP.CPA.09 for commercial, HIM.PA.154 for marketplace, CP.PMN.53 for Medicaid). Absent that documentation, such requests are considered not medically necessary.

Concurrent prescribing of tafamidis with agents on the policy’s excluded list (for example, Attruby) is not permitted. Such combination therapy will be considered not medically necessary unless exceptional, compelling documentation supporting safe and effective concurrent use is provided and the request satisfies any specific policy exceptions.

Product and Billing Codes

Product codesNDC

NDCs not listed

Product prescribing information referenced but specific NDCs not provided in this document

Maximum daily dose — Vyndaqel and Vyndamax maximum daily dosages

Vyndaqel (tafamidis meglumine)Maximum daily dose = 80 mg per day (4 capsules).

Vyndamax (tafamidis)Maximum daily dose = 61 mg per day (1 capsule).

Approval duration (related)Initial approval duration = 6 months (dose must not exceed labeled maximums).

Prior Authorization and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Vyndaqel/Vyndamax. The provider must submit documentation (e.g., office chart notes, laboratory results, imaging, hospitalization records) that supports the member has met all approval criteria before prior authorization will be granted.

Prior authorization required for initial and continuation therapy
Prescribers: treating clinician managing the member’s transthyretin amyloid cardiomyopathy

Documentation Required

Required Supporting Documentation

The following documentation is required to support the prior authorization request: clinical office notes documenting diagnosis and symptom history; recent hospitalization records (if applicable); results of laboratory testing including serum protein immunofixation, urine protein immunofixation, and serum free light chain (kappa/lambda) ratio; imaging and cardiac testing reports; and any relevant treatment history (including dates and response).

Background and Clinical Rationale

Transthyretin‑mediated cardiomyopathy (ATTR‑CM) results from deposition of misfolded transthyretin in the myocardium, causing progressive restrictive cardiomyopathy and heart‑failure symptoms. Tafamidis is a transthyretin stabilizer that binds to the thyroxine‑binding sites of transthyretin tetramers to reduce dissociation and amyloid formation, and is indicated to reduce cardiovascular mortality and cardiovascular‑related hospitalizations in adults with ATTR‑CM.

Because evidence for combining transthyretin‑targeted therapies is limited and evolving, the policy applies explicit concurrent‑use restrictions and documentation requirements when tafamidis is considered alongside other transthyretin‑lowering agents (see concurrent‑use section and Appendix D).

Key Definitions

Definition — cardiomyopathy of transthyretin-mediated amyloidosis (ATTR-CM)

Definition (term)cardiomyopathy of transthyretin-mediated amyloidosis (ATTR-CM): cardiomyopathy caused by deposition of transthyretin-derived amyloid in the heart, as defined in Appendix A.

Clinical relevanceIndication for tafamidis therapy when diagnostic criteria (biopsy or radionuclide imaging with negative monoclonal protein testing) are met.

AbbreviationsATTR-CM shown in policy appendices/acronym key; used throughout criteria and appendices.

Definition — New York Heart Association (heart failure functional class) (NYHA)

Definition (term)New York Heart Association (NHYA) functional class: standard heart-failure functional classification used in criteria; policy requires member to have NHYA Class I, II, or III for initial approval.

Use in criteria

Policy Summary

PayerCentene

PolicyClinical Policy: Tafamidis (Vyndaqel, Vyndamax)

Policy CodePolicy CP PHAR.432

Change TypeMaterial updates to concurrent-use exclusions and requirementsadded Attruby exclusion and conditional Amvuttra use

Effective DateSep 1, 2019

Next Review Date

SourceLink

On This Page

Denial Risk

Concurrent‑Use Restrictions

Concurrent use of Vyndaqel/Vyndamax with certain transthyretin‑lowering agents is restricted. Requests for concurrent prescribing with excluded agents will be denied. If concurrent use with a restricted agent is considered allowable under this policy, required specific documentation must be provided (see related callouts).

Vyndaqel/Vyndamax is not prescribed concurrently with Attruby (excluded)
Vyndaqel/Vyndamax is not prescribed concurrently with Onpattro (excluded)

Step Therapy

Step Requirement Before Concurrent Amvuttra Use

If a request seeks concurrent use of Vyndaqel/Vyndamax with Amvuttra (concurrent therapy rather than switching), the request must include documentation that the member had a positive but inadequate clinical response to Amvuttra monotherapy. Both of the following must be submitted: (a) documentation that the member experienced and maintained a positive response to Amvuttra monotherapy for at least 6 months, and (b) documentation that despite Amvuttra monotherapy the member continues to have clinically significant cardiac disease (for example ongoing cardiac‑related hospitalizations or persistent heart failure signs/symptoms). Requests that do not include this documentation may be denied.

Evidence of ≥6 months positive response to Amvuttra monotherapy
Evidence of continued clinical need despite Amvuttra (e.g., ongoing hospitalizations or persistent NYHA symptoms)
Requests for concurrent Amvuttra + Vyndaqel/Vyndamax without required documentation may be denied

Documentation Required

Concurrent Use Documentation Triggers

When concurrent‑use documentation is requested (for example, concurrent Amvuttra and Vyndaqel/Vyndamax), the provider must supply the specific supportive records described above. Failure to provide the required concurrent‑use documentation will be grounds for denial of the concurrent‑use request.

Concurrent‑use requests for Amvuttra require the positive‑but‑inadequate‑response documentation listed in this section
Absent or incomplete concurrent‑use documentation = denial risk

Definition — Concurrent use (as used in policy) definition and implications

Policy meaningConcurrent use refers to prescribing tafamidis (Vyndaqel/Vyndamax) at the same time as another transthyretin-targeting agent; policy specifies agents that are excluded and agents that may be allowed with conditions.

Excluded agentsAttruby is explicitly added to the list of agents excluded from concurrent use for initial and continued therapy; Onpattro also referenced in concurrent-use history.

Conditional concurrent useAmvuttra was removed from the excluded list per HELIOS-B evidence but concurrent use requires documentation of a prior positive yet inadequate response to Amvuttra monotherapy (at least 6 months and persistent need for cardiac-related hospitalization or clinical evidence).