This policy version was replaced August 28, 2023. To find the newest version, go to https://www.bluecrossmn.com/providers/medical-policy-and-utilization-management, read and accept the Blue Cross Medical Policy Statement, then select “Blue Cross and Blue Shield of Minnesota Medical Policies.” This will bring up the Medical Policy search screen. Enter the policy number without the version number (last 3 digits).

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive polyneuropathy affecting the peripheral and autonomic nervous system and occurs due to a point mutation of the transthyretin (TTR) gene. Vutrisiran is a transthyretin-directed small interfering ribonucleic acid (siRNA) that silences specific messenger RNA, blocking production of transthyretin protein. This process clears transthyretin amyloid deposits in peripheral tissues, restoring tissue function. Vutrisiran is administered by subcutaneous injection.

The U.S. Food and Drug Administration (FDA) has approved vutrisiran (Amvuttra™) for treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. Some safety concerns are noted with Amvuttra™, including arthralgia, dyspnea, and decrease in vitamin A. 

Definitions

Polyneuropathy disability (PND) score:

• I= sensory disturbance but preserved walking capacity
• II= impaired walking capacity but ability to walk without stick or crutches
• IIIa= walking with help of one stick or crutch
• IIIb= walking with help of 2 sticks or crutches 
• IV= confined to wheelchair or bedridden

Familial Amyloid Polyneuropathy (FAP) stage:

• 0= Asymptomatic
• 1= Unimpaired ambulation
• 2= Assistance with ambulation required 
• 3= Wheelchair bound or bedridden

I.    Initial Review for Vutrisiran (Amvuttra™)

Vutrisiran may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Age 18 years or older; AND
• Diagnosis of hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy; AND
• Genetic testing confirms a pathogenic transthyretin (TTR) mutation (e.g., V30M); AND
• ONE or more symptoms or physical findings attributable to hATTR amyloidosis with polyneuropathy, such as:
  • Peripheral/autonomic neuropathy;
  • Motor disability;
  • Cardiovascular dysfunction;
  • Renal dysfunction; 
• AND
• ONE of the following:
  • Baseline polyneuropathy disability (PND) score ≤ IIIb; OR
  • Familial amyloid polyneuropathy (FAP) Stage 1 or 2;
• AND
• Not used in combination with oligonucleotide agents (e.g., patisiran, inotersen) or tafamidis meglumine; AND
• No FDA labeled contraindications to vutrisiran (see table 1 below); AND
• The dose is within the FDA labeled dose (see table 2 below); AND
• For commercial health plan members only, vutrisiran is administered in accordance with site of service criteria (see policy XI-06).

II.   Renewal Review for Vutrisiran (Amvuttra™)

Vutrisiran may be considered MEDICALLY NECESSARY AND APPROPRIATE when ALL of the following criteria are met:

• Previously approved for vutrisiran through the initial review process; AND
• Continued positive clinical response to vutrisiran (e.g., improved neurologic function, improved motor function, improved cardiac function, stabilization and/or slowing of disease progression); AND
• Not used in combination with oligonucleotide agents (e.g., patisiran, inotersen) or tafamidis meglumine; AND
• No FDA labeled contraindications to vutrisiran (see table 1 below); AND
• The dose is within the FDA labeled dose (see table 2 below); AND
• For commercial health plan members only, vutrisiran is administered in accordance with site of service criteria (see policy XI-06).

III.  Experimental/Investigative Uses

All other uses of vutrisiran are considered EXPERIMENTAL/INVESTIGATIVE due to the lack of clinical evidence demonstrating an impact on improved health outcomes.

Table 1.  FDA Labeled Contraindications

Table 2. Dosing

NOTE:  See documentation submission requirements below if the requested dose is higher or more frequent than the dosing criteria provided in this table.

Documentation Submission:

Documentation supporting the medical necessity criteria described in the policy must be included in the prior authorization, when prior authorization is required. In addition, the following documentation must also be submitted:

Initial Review

1. Clinical notes describing the diagnosis and clinical features of the diagnosis.
2. Laboratory documentation confirming diagnosis of polyneuropathy of hereditary transthyretin-mediated amyloidosis.
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
4. For commercial health plan members only, the site of service for vutrisiran administration is specified, including CMS place of service code (see policy XI-06). If vutrisiran is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.

Renewal Review

1. Documentation of prior approval for the requested agent through the initial review process.
2. Documentation, since most recent approval, supporting positive continued positive clinical response.
3. The dose being requested. If the requested dose is higher or more frequent than the dosing guidelines provided in the table above, a clear explanation for the medical necessity of the requested dose MUST be submitted, including prior dosing (strength and frequency) associated with inadequate response.
4. For commercial health plan members only, the site of service for vutrisiran administration is specified, including CMS place of service code (see policy XI-06). If vutrisiran is administered in a hospital outpatient facility, a clear explanation for the medical necessity of the site of service MUST be submitted, including documentation for one or more of the site of service criteria provided in policy XI-06.