Coverage Policy Manual
Policy #: 2020003
Category: Pharmacy
Initiated: February 2020
Last Review: January 2024
  Tafamidis (e.g., Vyndamax)
Description:
Tafamidis/Tafamidis Meglumine are selective transthyretin (TTR) stabilizers and are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Transthyretin protein binds and transports less than 10% of circulating thyroxine (T4). It also binds holo-retinol-binding protein (retinol-binding protein-vitamin A complex) and facilitates the transport of retinol to tissues; TTR is the only known holo-retinol binding protein transporter.
 
Regulatory Status
 
Tafamidis (e.g., Vyndamax®) and Tafamidis Meglumine (e.g., Vyndagel) were approved by the FDA on May 3, 2019, for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.  
 
Coding
 
See CPT/HCPCS Code section.
 
Policy/
Coverage:
The use of Tafamidis and Tafamidis Meglumine is not covered under the medical benefit.  
 
The use of Tafamidis and Tafamidis Meglumine is addressed under the Pharmacy benefit for those plans that utilize the ABCBS pharmacy benefit.  
 
Effective January 10, 2024
 
Meets primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Tafamidis/Tafamidis Meglumine meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization when ALL the following are met:
 
INITIAL APPROVAL for 6 months:
 
1. Diagnosis of cardiomyopathy due to hereditary transthyretin amyloidosis (hATTR) OR wild type transthyretin amyloidosis (ATTRwt) – documentation from the medical record must be provided in the form of one of the following (Maurer, 2018):
a. Presence of amyloid deposits in biopsy tissue – laboratory documentation must be provided; OR
b. Presence of a variant TTR genotype and/or TTR precursor protein identification by:
i. Immunohistochemistry or mass spectrometry of a biopsy specimen; OR    
ii. Positive scintigraphy (99m Tc-pyrophosphate), with a *semi-quantitative visual score (Myocardial Uptake by Comparison to Bone of 2 or 3, or Heart-to-Contralateral Lung Ratio (H/CL) of > 1.5.
 
*Semi –quantitative visual grading of myocardia 99m Tc-PYP Uptake by Comparison to Bone (rib) Uptake:
Grade 0—no myocardial uptake and normal rib uptake
Grade 1—myocardial uptake less than rib uptake
Grade 2—myocardial uptake equal to rib uptake
Grade 3—myocardial uptake greater than rib uptake with mild/absent rib uptake; AND
 
2. Current or historical evidence for NYHA Class I, II, or III heart failure (HF), including either (Maurer, 2018):
a.  At least 1 prior hospitalization for HF with clinical evidence of HF manifested by signs or symptoms of:
i.  Volume overload (Maurer, 2018); OR
ii. Elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement)(Maurer, 2018) – documentation from the medical record must be provided; OR
b. Submission of lab report showing NT-pro BNP > 600 (Maurer, 2018);  AND
3. Submission of Echocardiogram results demonstrating an End-diastolic interventricular septal wall thickness is greater than 12 mm – documentation from the medical record must be provided (Maurer, 2018); AND
4. Primary (light chain) amyloidosis has been excluded by serum and urine immunofixation and serum free light chain assay (Maurer, 2018); AND
5. Must not be taking concurrently with inotersen or patisiran; AND
6. Individual does not have any of the following conditions:
a. Class 4 heart failure; OR
b. Prior liver transplantation; OR
c. Prior heart transplantation; OR
d. In combination with inotersen (e.g., Tegsedi) or patisiran (e.g., Onpattro); AND
7.  Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL:
 
1. Prior approval by Arkansas Blue Cross in the past two years, or the member currently meets all the coverage criteria.
2. Description of a clinically meaningful beneficial response to treatment with tafamidis such as improvement or slowing of progression of exercise intolerance, BNP, or fluid overload compared to baseline – documentation from the medical record must be provided.
3. Submission of current results of NT-pro BNP.  
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dosage of Tafamidis (e.g., Vyndamax) is 61 mg (one capsule) once daily.
 
The recommended dosage of Tafamidis Meglumine (e.g., Vyndaqel) is 80 mg (four 20mg capsules) daily.
 
Tafamidis meglumine is available as 20 mg tablets and tafamidis is available as 61 mg.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Tafamidis or Tafamidis Meglumine, for any indication or circumstance not described above, does not meet primary certificate coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, Tafamidis or Tafamidis Meglumine, for any indication or circumstance not described above, is considered investigational.   
 
Investigational services are specific to contract exclusions in most member benefit certificates of coverage.
 
Effective February 15, 2023 to January 9, 2024
 
Meets primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Tafamidis/Tafamidis Meglumine meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization when ALL of the following are met:
 
Initial approval for 6 months if ALL of the following criteria met:
 
    1. Diagnosis of cardiomyopathy due to hereditary transthyretin amyloidosis (hATTR) OR wild type transthyretin amyloidosis (ATTRwt) – documentation from the medical record must be provided in the form of one of the following (Maurer, 2018):  
a. Presence of amyloid deposits in biopsy tissue – laboratory documentation must be provided; OR
b. Presence of a variant TTR genotype and/or TTR precursor protein identification by
i. Immunohistochemistry or mass spectrometry of a biopsy specimen; OR    
ii. Positive scintigraphy (99m Tc-pyrophosphate), with a *semi-quantitative visual score (Myocardial Uptake by Comparison to Bone of 2 or 3, or Heart-to-Contralateral Lung Ratio (H/CL) of > 1.5.
 
*Semi –quantitative visual grading of myocardia 99m Tc-PYP Uptake by Comparison to Bone (rib) Uptake:
Grade 0—no myocardial uptake and normal rib uptake
Grade 1—myocardial uptake less than rib uptake
Grade 2—myocardial uptake equal to rib uptake
Grade 3—myocardial uptake greater than rib uptake with mild/absent rib uptake AND
 
2. Current or historical evidence for NYHA Class I, II, or III heart failure (HF), including either (Maurer, 2018):
a. At least 1 prior hospitalization for HF with clinical evidence of HF manifested by signs or symptoms of:
i. Volume overload (Maurer, 2018); OR
ii. Elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement)(Maurer, 2018) – documentation from the medical record must be provided; OR
b. Submission of lab report showing NT-pro BNP > 600 (Maurer, 2018);  AND
 
3. Submission of Echocardiogram results demonstrating an End-diastolic interventricular septal wall thickness is greater than 12 mm – documentation from the medical record must be provided (Maurer, 2018); AND
 
4. Primary (light chain) amyloidosis has been excluded by serum and urine immunofixation and serum free light chain assay (Maurer, 2018); AND
 
5. Must not be taking concurrently with inotersen or patisiran AND
 
6. Must be dosed in accordance with the FDA label.
 
Concurrent review will require:
 
    1. Prior approval by Arkansas Blue Cross in the past two years, or the member currently meets all the coverage criteria.
 
2. Description of a clinically meaningful beneficial response to treatment with tafamidis such as improvement or slowing of progression of exercise intolerance, BNP, or fluid overload compared to baseline – documentation from the medical record must be provided
 
3. Submission of current results of NT-pro BNP  
 
Dosage and administration
Dosing per FDA Guidelines
 
The recommended dosage of Tafamidis (e.g., Vyndamax) is 61 mg (one capsule) once daily.
 
The recommended dosage of Tafamidis Meglumine (e.g., Vyndaqel) is 80 mg (four 20mg capsules) daily.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Tafamidis or Tafamidis Meglumine does not meet primary certificate coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for any other indications including the following:
 
    1. Class 4 heart failure
    2. Prior liver transplantation
    3. Prior heart transplantation
    4. In combination with inotersen (e.g., Tegsedi) or patisairan (e.g., Onpattro)
 
For members with contracts without primary coverage criteria, Tafamidis or Tafamidis Meglumine are considered investigational including the following:
 
    1. Class 4 heart failure
    2. Prior liver transplantation
    3. Prior heart transplantation
    4. In combination with inotersen (e.g., Tegsedi) or patisiran (e.g., Onpattro)
 
Investigational services are specific to contract exclusions in most member benefit certificates of coverage.
 
Effective February 9, 2022 to February 14, 2023
 
Tafamidis/Tafamidis Meglumine Meets primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of Tafamidis/Tafamidis Meglumine meets member benefit primary coverage criteria for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization when ALL of the following are met:
 
Initial approval for 6 months if ALL of the following criteria met:
 
    1. Diagnosis of cardiomyopathy due to hereditary transthyretin amyloidosis (hATTR) OR wild type transthyretin amyloidosis (ATTRwt) – documentation from the medical record must be provided in the form of one of the following (Maurer, 2018):  
        • Presence of amyloid deposits in biopsy tissue – laboratory documentation must be provided; OR
        • Presence of a variant TTR genotype and/or TTR precursor protein identification by
            1. Immunohistochemistry or mass spectrometry of a biopsy specimen; OR
            2. Positive scintigraphy (99m Tc-pyrophosphate), with a *semi-quantitative visual score (Myocardial Uptake by Comparison to Bone of 2 or 3, or Heart-to-Contralateral Lung Ratio (H/CL) of > 1.5.
*Semi –quantitative visual grading of myocardia 99m Tc-PYP Uptake by Comparison to Bone (rib) Uptake:
Grade 0—no myocardial uptake and normal rib uptake
Grade 1—myocardial uptake less than rib uptake
Grade 2—myocardial uptake equal to rib uptake
Grade 3—myocardial uptake greater than rib uptake with mild/absent rib uptake
 AND
 
2. Current or historical evidence for NYHA Class I, II, or III heart failure (HF), including either (Maurer, 2018):
        • At least 1 prior hospitalization for HF with clinical evidence of HF manifested by signs or symptoms of:
            1. Volume overload (Maurer, 2018); OR
            2. Elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement)(Maurer, 2018) – documentation from the medical record must be provided; OR
        •  Submission of lab report showing NT-pro BNP > 600 (Maurer, 2018);  AND
 
3. Submission of Echocardiogram results demonstrating an End-diastolic interventricular septal wall thickness is greater than 12 mm – documentation from the medical record must be provided (Maurer, 2018); AND
 
4. Primary (light chain) amyloidosis has been excluded by serum and urine immunofixation and serum free light chain assay (Maurer, 2018); AND
 
5. Must not be taking concurrently with inotersen or patisiran
 
Concurrent review will require:
 
    1. Prior approval by Arkansas Blue Cross in the past two years, or the member currently meets all the coverage criteria.
 
2. Description of a clinically meaningful beneficial response to treatment with tafamidis such as improvement or slowing of progression of exercise intolerance, BNP, or fluid overload compared to baseline – documentation from the medical record must be provided
 
3. Submission of current results of NT-pro BNP  
 
Dosage and administration
 
The recommended dosage of Tafamidis (Vyndamax) is 61 mg (one capsule) once daily.
 
The recommended dosage of Tafamidis Meglumine (Vyndaqel) is 80 mg (four 20mg capsules) daily.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Tafamidis or Tafamidis Meglumine does not meet primary coverage criteria that there be scientific evidence of effectiveness for any other indications including the following situations:
 
      • Class 4 heart failure
      • Prior liver transplantation
      • Prior heart transplantation
      • In combination with inotersen (Tegsedi) or patisairan (Onpattro)
 
For members with contracts without primary coverage criteria, Tafamidis or Tafamidis Meglumine are considered investigational.  
 
Investigational services are specific to contract exclusions in most member benefit certificates of coverage.  
 
Effective February 1, 2020 to February 8, 2022
 
Tafamidis/Tafamidis Meglumine Meets primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of Tafamidis/Tafamidis Meglumine meets member benefit primary coverage criteria for the treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization when ALL of the following are met:
 
Initial approval for 6 months if ALL of the following criteria met:
 
    1. Diagnosis of cardiomyopathy due to hereditary transthyretin amyloidosis (hATTR) OR wild type transthyretin amyloidosis (ATTRwt) – documentation from the medical record must be provided in the form of one of the following (Maurer, 2018):  
        • Presence of amyloid deposits in biopsy tissue – laboratory documentation must be provided; OR
        • Presence of a variant TTR genotype and/or TTR precursor protein identification by
            1. Immunohistochemistry or mass spectrometry of a biopsy specimen; OR
            2. Positive scintigraphy (99m Tc-pyrophosphate), with a *semi-quantitative visual score (Myocardial Uptake by Comparison to Bone of 2 or 3, or Heart-to-Contralateral Lung Ratio (H/CL) of > 1.5.
*Semi –quantitative visual grading of myocardia 99m Tc-PYP Uptake by Comparison to Bone (rib) Uptake:
Grade 0—no myocardial uptake and normal rib uptake
Grade 1—myocardial uptake less than rib uptake
Grade 2—myocardial uptake equal to rib uptake
Grade 3—myocardial uptake greater than rib uptake with mild/absent rib uptake
 AND
 
2. Current or historical evidence for NYHA Class I, II, or III heart failure (HF), including either (Maurer, 2018):
        • At least 1 prior hospitalization for HF with clinical evidence of HF manifested by signs or symptoms of:
            1. Volume overload (Maurer, 2018); OR
            2. Elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that required/requires treatment with a diuretic for improvement)(Maurer, 2018) – documentation from the medical record must be provided; OR
        •  Submission of lab report showing NT-pro BNP > 600 (Maurer, 2018);  AND
 
3. Submission of Echocardiogram results demonstrating an End-diastolic interventricular septal wall thickness is greater than 12 mm – documentation from the medical record must be provided (Maurer, 2018); AND
 
4. Primary (light chain) amyloidosis has been excluded by serum and urine immunofixation and serum free light chain assay (Maurer, 2018); AND
 
5. Must not be taking concurrently with inotersen or patisiran
 
Concurrent review will require:
 
    1. Prior approval by Arkansas Blue Cross in the past two years, or the member currently meets all the coverage criteria.
 
2. Description of a clinically meaningful beneficial response to treatment with tafamidis such as improvement or slowing of progression of exercise intolerance, BNP, or fluid overload compared to baseline – documentation from the medical record must be provided
 
3. Submission of current results of NT-pro BNP  
 
Dosage and administration
 
The recommended dosage of Tafamidis (Vyndamax) is 61 mg (one capsule) once daily.
 
The recommended dosage of Tafamidis Meglumine (Vyndaqel) is 80 mg (four 20mg capsules) daily.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
The use of Tafamidis or Tafamidis Meglumine does not meet primary coverage criteria that there be scientific evidence of effectiveness for any other indications including the following situations:
 
      • Class 4 heart failure
      • Prior liver transplantation
      • Prior heart transplantation
      • In combination with inotersen (Tegsedi) or patisairan (Onpattro)
 
For members with contracts without primary coverage criteria, Tafamidis or Tafamidis Meglumine are considered investigational.  
 
Investigational services are specific to contract exclusions in most member benefit certificates of coverage.  
Rationale:
The safety and efficacy of Tafamidis in slowing progression of transthyretin-mediated cardiac amyloidosis was demonstrated in a multicenter, international, randomized, double-blind, placebo-controlled study in 441 patients with wild type or hereditary ATTR-CM.
 
Patients were randomized in a 1:2:2 ratio to receive Tafamidis 20 mg (n=88), Tafamidis 80 mg (administered as four 20-mg Tafamidis capsules) (n=176), or matching placebo (n=177) once daily for 30 months, in addition to standard of care (e.g., diuretics). Treatment assignment was stratified by the presence or absence of a variant TTR genotype as well as baseline disease severity (NYHA Class). Patients between 18-90 years of age were eligible to participate if they had hATTR or ATTRwt confirmed by the presence of amyloid deposits on analysis of biopsy specimens (cardiac or noncardiac sites) or by the presence of transthyretin precursor protein confirmed on immunohistochemical analysis, scintigraphy, or mass spectrometry. Cardiac involvement was confirmed by an end-diastolic interventricular septal wall thickness exceeding 12mm, a history of heart failure with at least one prior hospitalization for heart failure or clinical evidence of heart failure, an N-terminal99 pro-B-type natriuretic peptide level greater than or equal to 600pg per millimeter, and a 6-minute walk test distance exceeding 100 meters. Transplant patients and patients with primary (light chain) amyloidosis were excluded from this study.
 
Primary analysis demonstrated a significant reduction (p=0.0006) in all-cause mortality and frequency of cardiovascular-related hospitalizations in the pooled Tafamidis 20-mg and 80-mg groups versus placebo. Tafamidis was associated with lower all-cause mortality than placebo (78 of 264 [29.5%] vs. 76 of 177 [42.9%]. At month 30, tafamidis was also associated with a lower rate of decline in distance for the 6-minute walk test (P<0.001) and a lower rate of decline in KCCQ-OS score (P<0.001). The incidence and types of adverse events were similar in the two groups.
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) showed that tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to estimate the impact of tafamidis on survival and quality-adjusted life-years (QALYs).
 
A multi-state, cohort, Markov model was developed to simulate the disease course of ATTR-CM throughout a lifetime. For survival extrapolation, survival curves were fitted by treatment arm and New York Heart Association (NYHA) Class I/II (68% of patients) and NYHA Class III (32% of patients) cohorts using the individual patient-level data from both the ATTR-ACT and the corresponding long-term extension study. Univariate and multivariate sensitivity analyses were conducted. The predicted mean survival for the total population (NYHA Class I/II + III) was 6.73 years for tafamidis and 2.85 years for the standard of care (SoC), resulting in an incremental mean survival of 3.88 years [95% confidence interval (CI) 1.32-5.66]. Of the 6.73 life-years, patients on tafamidis spend, on average, 4.82 years in NYHA Class I/II, while patients on SoC spend an average of 1.60 life-years in these classes. The combination of longer survival in lower NYHA classes produced a QALY gain of 5.39 for tafamidis and 2.11 for SoC, resulting in 3.29 incremental QALYs (95% CI 1.21-4.74) in favor of tafamidis.
 
Based on the disease simulation model results, tafamidis is expected to more than double the life expectancy and QALYs of ATTR-CM patients compared to SoC. Longer-term follow-up data from the ATTR-ACT extension study will further inform these findings. (Rozenbaum MH, Garcia A, Grima D, 2022)
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
J9349Injection, tafasitamab-cxix, 2 mg
References: American Society of Nuclear Cardiology.(2019) ASNC Cardiac Amyloidosis Practice Points. www.asnc.org. Updated Feb 2019. Accessed Jan 16, 2020.

Damy T, Garcia-Pavia P, Hanna M, Judge DP, Merlini G, Gundapaneni B, Patterson TA, Riley S, Schwartz JH, Sultan MB, Witteles R.(2021) Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Eur J Heart Fail. 2021 Feb;23(2):277-285. doi: 10.1002/ejhf.2027. Epub 2020 Nov 12. PMID: 33070419; PMCID: PMC8048553.

Maurer MS, Schwartz JH, Gundapaneni B, et al.(2018) Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med 2018 Sep 13;379(11):1007-1016. doi 10.1056/NEJMoa1805689. Epub 2018 Aug 27.

Rozenbaum MH, Garcia A, Grima D, Tran D, Bhambri R, Stewart M, Li B, Heeg B, Postma M, Masri A.(2022) Health impact of tafamidis in transthyretin amyloid cardiomyopathy patients: an analysis from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and the open-label long-term extension studies. Eur Heart J Qual Care Clin Outcomes. 2022 Aug 17;8(5):529-538. doi: 10.1093/ehjqcco/qcab031. PMID: 33895806; PMCID: PMC9382662.

Vyndaqel and Vyndamax [package insert].(2019) Vyndaqel and Vyndamax New York, NY: Pfizer Labs.; May 2019
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2024 American Medical Association.