Amvuttra (vutrisiran) — HCPCS J0225

hATTR / ATTR-CM treatment landscape FDA verified May 2026

Five disease-modifying therapies span two related indications — hereditary polyneuropathy (hATTR-PN) and cardiomyopathy (ATTR-CM, wild-type or hereditary).

Transthyretin amyloidosis (ATTR) is a progressive multisystem disease driven by misfolded TTR protein depositing in nerves (hATTR-PN) and heart (ATTR-CM). Modern therapy attacks TTR three ways: silence the gene (siRNA / antisense), stabilize the tetramer (tafamidis), or extract amyloid (early-stage research). Amvuttra is unique in covering both hATTR-PN and ATTR-CM with q3mo SC dosing.

Onpattro vs Amvuttra — same target, very different billing Reviewed May 2026

Both are Alnylam siRNA therapeutics targeting TTR mRNA. Different formulations, different J-codes, dramatically different patient experience.

Onpattro (patisiran, J0222) was the first FDA-approved siRNA drug ever (August 2018). Amvuttra (vutrisiran, J0225) followed in June 2022 and added the GalNAc N-acetylgalactosamine conjugate, which targets vutrisiran directly to hepatocyte ASGPR receptors. This enables far more efficient hepatic uptake and dramatically extended dosing interval — from q3wk IV to q3mo SC. Most Onpattro patients have transitioned to Amvuttra due to convenience.

ATTR-CM 2025 indication expansion (HELIOS-B) FDA verified Mar 2025

The major billing growth driver for J0225 — ATTR cardiomyopathy is far more prevalent than hATTR-PN.

In March 2025, FDA expanded the Amvuttra label to include treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart-failure visits. The approval was based on the Phase 3 HELIOS-B trial (NCT04153149), which enrolled 655 ATTR-CM patients and demonstrated:

• Reduction in all-cause mortality and recurrent cardiovascular events vs placebo
• Benefit observed across both wild-type (ATTRwt) and hereditary (ATTRv) ATTR-CM populations
• Benefit observed both as monotherapy and in patients on background tafamidis
• Functional and quality-of-life improvements (KCCQ, 6MWT)

Why this matters for billing

Wild-type ATTR-CM is increasingly recognized in older patients (typically men >65) and is dramatically more prevalent than hATTR-PN. Cardiology adoption of Amvuttra is rapidly expanding the J0225 claim volume. Cardiologists, not just neurologists, now write Amvuttra prescriptions.

ATTR-CM diagnostic workup (required for PA)

• Cardiac amyloid imaging: Technetium-99m pyrophosphate (PYP) scan with grade 2 or 3 uptake (Perugini grade) — CPT 78803 (planar) + 78803-26 if separate interpretation, or 78813/78814 (PET/CT). Alternative: endomyocardial biopsy with Congo red staining and TTR confirmation by mass spec or IHC.
• Plasma cell dyscrasia exclusion: SPEP (CPT 84165), UPEP (84166), serum free light chain assay (83883) — required to rule out AL amyloidosis, which can mimic ATTR-CM clinically and on PYP imaging.
• TTR genetic testing (CPT 81404): distinguishes hereditary (ATTRv) from wild-type (ATTRwt) ATTR-CM. Both are covered by the indication, but genetic status affects family counseling.
• Cardiac biomarkers: NT-proBNP, troponin (for staging and monitoring).
• NYHA class: Most payers cover NYHA I–III; some restrict NYHA IV based on HELIOS-B inclusion criteria.

Dosing & unit math FDA label 2025

Fixed-dose, q3mo SC. The simplest specialty drug dosing schedule on the formulary.

Adult dosing (both indications)

• 25 mg subcutaneously every 3 months (every 12 weeks) — fixed dose, NOT weight-based
• Single 25 mg / 0.5 mL prefilled syringe per dose
• Administered by HCP in clinic; abdomen, thigh, or upper arm; rotate sites
• 1 mg = 1 unit — bill 25 units per dose
• 4 doses per year — total annual J0225 units = 100
• If a dose is missed, administer as soon as possible and resume on the original schedule

Worked example — first-year billing for a hATTR-PN or ATTR-CM patient

No premedication required

Unlike Onpattro — which requires a 4-agent IV premedication regimen (corticosteroid + acetaminophen + H1 antihistamine + H2 antihistamine) before each q3wk infusion — Amvuttra requires no premedication. This eliminates ~60–90 minutes of pre-infusion time and reduces nursing burden substantially. Combined with the q3mo schedule, total clinic time per year drops dramatically.

TTR genetic testing requirement Verified May 2026

Required for hATTR-PN PA; recommended for ATTR-CM to distinguish wild-type vs hereditary.

For the hATTR-PN indication, payer PA criteria require documented pathogenic variant in the TTR gene. Common variants: V30M (Val122Ile), T60A, L55P, and others. TTR full gene sequencing identifies the specific mutation.

Vitamin A supplementation requirement FDA label 2025

Vutrisiran reduces serum vitamin A (retinol) levels by ~70% because TTR is the primary plasma transporter of retinol-binding protein (RBP4) bound to vitamin A. The FDA label requires oral supplementation with approximately 2,500 IU of vitamin A per day during therapy.

• Standard dose: 2,500 IU/day vitamin A (retinyl palmitate or beta-carotene equivalent)
• Available OTC; not part of the medical drug claim — document supplementation in chart
• Refer patient to ophthalmology if visual symptoms develop (e.g., night vision changes)
• Do NOT exceed 2,500 IU/day — higher doses do not normalize serum levels (RBP4 is the limiting factor) and may increase teratogenic risk in pregnancy

NDC reference FDA NDC Directory verified May 2026

Administration codes CPT verified May 2026

Vutrisiran is a non-chemotherapy subcutaneous injection by HCP — 96372 is the correct admin code.

Modifiers CMS verified May 2026

JZ — required on virtually every claim

Effective July 1, 2023, CMS requires the JZ modifier on all single-dose container claims when no drug is discarded. Amvuttra ships as a 25 mg/0.5 mL single-dose prefilled syringe, and the full 25 mg dose is administered with no waste. JZ applies on virtually every J0225 claim.

JW — not typically applicable

Amvuttra is a fixed dose delivered as a single-dose prefilled syringe. There is no partial-dose or weight-based scenario in adults that would generate single-dose container waste. JW would apply only in the unusual circumstance of a damaged syringe before any drug was administered — in which case follow your practice's product replacement policy via Alnylam Assist before billing JW.

Modifier 25 — same-day E/M

Use modifier 25 on the E/M code when a significant, separately identifiable evaluation and management service is performed on the same day as the injection. For ATTR-CM patients, the q3mo dosing visit is often paired with a focused cardiology follow-up — modifier 25 may be appropriate when documentation supports a separate E/M.

340B modifiers (JG, TB)

For 340B-acquired Amvuttra, follow your MAC's current 340B modifier policy. Alnylam's billing guide does not provide 340B-specific instructions for J0225.

ICD-10-CM by indication FY2026 verified May 2026

Two indication families. Use the most specific code supported by encounter documentation.

Site of care & place of service Verified May 2026

Because Amvuttra is a 1–2 minute SC injection with no premedication, it is well-suited to physician office and clinic settings. Some payer policies allow home administration in select markets via specialty infusion vendors. Hospital outpatient is generally not necessary and may be disfavored by commercial site-of-care UM.

Claim form field mapping Alnylam Mar 2026

From Alnylam Assist HCP coding & reimbursement materials.

Payer policy snapshot Reviewed May 2026

All major payers require PA. Workup completeness drives approval speed.

Required PA documentation

• hATTR-PN: Specialist diagnosis (neurology), TTR genetic testing report with pathogenic variant, EMG/NCS or other neuropathy documentation, baseline mNIS+7 or NIS-LL when available
• ATTR-CM: Specialist diagnosis (cardiology, ideally amyloid program), PYP scan with Perugini grade 2 or 3 (or endomyocardial biopsy with TTR confirmation), negative SPEP/UPEP/serum free light chains, NT-proBNP, troponin, NYHA class, echo (LV wall thickness), TTR genetic testing
• Vitamin A supplementation plan documented in chart
• Site of care & administering provider information

Step therapy

Generally not required for first-line use in either indication. Some payers require prior tafamidis trial or contraindication for ATTR-CM, but this is not universal — HELIOS-B included patients on background tafamidis and demonstrated benefit, supporting Amvuttra as a primary or add-on therapy.

Medicare reimbursement CMS Q2 2026 (live)

Quarterly ASP from CMS Part B Drug Pricing File. Refreshes automatically each quarter.

Coverage

No NCD specific to vutrisiran. Coverage falls under MAC LCDs for biologics and the generic drug-coverage framework. All MACs cover J0225 for FDA-approved on-label indications (hATTR-PN since 2022; ATTR-CM since March 2025) with appropriate ICD-10 and workup documentation.

Code history

• J0225 — permanent code, "Injection, vutrisiran, 1 mg." Pre-permanent-code period used unclassified J3490 with manufacturer NDC.

Patient assistance — Alnylam Assist Alnylam verified May 2026

• Alnylam Assist: 1-833-256-2748 / alnylam.com/alnylam-assist — benefits investigation, prior authorization assistance, appeal support, dosing logistics
• Alnylam Assist Co-Pay Program: commercial copay support for eligible commercially-insured patients (excludes Medicare, Medicaid, federal program patients)
• Alnylam Patient Foundation: independent 501(c)(3) providing free product for uninsured / underinsured patients meeting income requirements
• Foundations: for Medicare patients, refer to PAN Foundation, HealthWell Foundation — verify open hATTR / ATTR-CM funds quarterly (these funds open and close based on grant cycles)
• Same patient assistance program covers Onpattro and Amvuttra; transitioning patients can stay on the same support pathway

Common denials & how to fix them

Frequently asked questions

What is the HCPCS code for Amvuttra?

Amvuttra (vutrisiran) is billed under HCPCS J0225 — "Injection, vutrisiran, 1 mg." Each milligram equals one billable unit, so the standard 25 mg subcutaneous dose is billed as 25 units. J0225 is a permanent code. Amvuttra is administered subcutaneously once every 3 months — only 4 doses per year.

How many units do I bill for an Amvuttra dose?

Bill 25 units of J0225 per dose. Amvuttra ships as a 25 mg/0.5 mL single-dose prefilled syringe — fixed dose, not weight-based. Annual billing per patient: 4 doses × 25 units = 100 units per year. JZ modifier applies on every claim (no waste).

What administration CPT do I use for Amvuttra?

CPT 96372 — therapeutic SC/IM injection, non-chemo. Do NOT bill 96365 (therapeutic IV; wrong route) or 96413 (chemotherapy admin; wrong drug class). Vutrisiran is a clinic-administered SC injection of a non-chemotherapy biologic, so 96372 is the correct code.

What is the dosing schedule for Amvuttra?

25 mg subcutaneously every 3 months (every 12 weeks) — only 4 doses per year. Fixed dose, not weight-based. No premedication required. Vitamin A 2,500 IU/day oral supplementation is required during therapy.

What are the FDA-approved indications for Amvuttra?

Two indications: (1) polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults — original 2022 FDA approval; (2) cardiomyopathy of wild-type or hereditary ATTR (ATTR-CM) in adults — added March 2025 based on the HELIOS-B trial. The 2025 ATTR-CM expansion is a major billing growth driver because ATTR-CM has a much larger prevalent population than hATTR-PN.

Is genetic testing required for Amvuttra?

For hATTR-PN: yes — TTR gene mutation analysis (CPT 81404) is required by all major payers' PA criteria. For ATTR-CM: TTR genetic testing distinguishes hereditary vs wild-type but the indication covers both. ATTR-CM PA additionally requires cardiac amyloid imaging (PYP scan with Perugini grade 2 or 3) or endomyocardial biopsy AND a plasma cell dyscrasia workup (SPEP/UPEP/free light chains) to exclude AL amyloidosis.

What is the Medicare reimbursement for J0225?

For Q2 2026, the Medicare Part B payment limit for J0225 is $5,019.273 per mg (ASP + 6%). Each 25 mg dose reimburses at approximately $125,481.83. Annualized cost (Medicare ASP+6%): ~$501,927 for 4 doses/year. Sequestration (~2%) reduces actual paid to roughly ASP + 4.3%. ASP is updated quarterly.

Should patients on Onpattro be switched to Amvuttra?

In practice, most Onpattro patients have already been transitioned to Amvuttra due to dramatically better convenience: q3mo SC injection vs q3wk IV infusion with 4-agent premedication. Both are Alnylam siRNA therapeutics targeting TTR mRNA, but vutrisiran's GalNAc conjugate enables hepatocyte-targeted delivery and the q3mo dosing interval. Switching requires a fresh PA submission (different J-code, different formulation). Onpattro remains FDA-approved only for hATTR-PN; Amvuttra now covers both hATTR-PN and ATTR-CM.

Why is vitamin A supplementation required?

TTR is the primary plasma transporter of retinol-binding protein bound to vitamin A. Vutrisiran knocks down TTR by ~80–90%, which reduces serum vitamin A by ~70%. The FDA label requires 2,500 IU/day oral vitamin A supplementation during therapy. Do not exceed 2,500 IU/day — higher doses do not normalize serum levels (RBP4 is the limiting factor) and may increase teratogenic risk in pregnancy. Same supplementation rule applies to Onpattro.

Source documents

1. Alnylam Assist — Amvuttra HCP coding & reimbursement
   Manufacturer billing and access support resources, verified May 2026
2. DailyMed — AMVUTTRA (vutrisiran) Prescribing Information
   FDA-approved label, most recent revision incorporates HELIOS-B ATTR-CM expansion (March 2025)
3. FDA Amvuttra label PDF (NDA 215515)
   Original hATTR-PN approval June 13, 2022; ATTR-CM expansion 2025
4. HELIOS-B trial — Vutrisiran for ATTR Cardiomyopathy (NEJM)
   Phase 3 ATTR-CM trial supporting 2025 indication expansion
5. CMS — Medicare Part B Drug ASP Pricing File
   Q2 2026 quarterly file, effective April 1 – June 30, 2026
6. SEER CanMED — HCPCS J0225 reference
7. UnitedHealthcare — Medical Drug Coverage Policy (vutrisiran)
8. Aetna — Clinical Policy Bulletins (transthyretin amyloidosis treatments)
9. American Academy of Neurology (AAN) — hATTR practice guidance
10. AHA / ACC — Cardiac Amyloidosis Diagnosis & Treatment Scientific Statement
11. FDA National Drug Code Directory

About this page

We maintain this page as a living reference. Medicare ASP pricing is bound to our underlying CareCost data layer and refreshes automatically when CMS publishes new quarterly files. Coding and policy content is reviewed at least quarterly and updated whenever a source document changes.

Found an error? Email hello@carecostestimate.com.

Refresh cadence

Reviewer

Change log

• May 2, 2026 — Initial publication. ASP data: Q2 2026. Manufacturer source: Alnylam Assist Mar 2026. FDA label: most recent revision incorporates March 2025 HELIOS-B ATTR-CM expansion. hATTR-PN + ATTR-CM coverage. Onpattro vs Amvuttra comparison + treatment landscape table.

Methodology

Every claim on this page is sourced inline. Pricing reflects the current CMS Part B Drug ASP Pricing File. Payer policies are read directly from each payer's published medical/pharmacy policy documents. Indication list is verified against the current FDA label revision. We do not paraphrase from billing-software vendor blogs.