Onpattro (patisiran) — HCPCS J0222

hATTR amyloidosis treatment landscape AAN guidelines verified Apr 2026

Hereditary transthyretin-mediated amyloidosis (hATTR) is rare, progressive, and now has multiple disease-modifying options. Treatment selection drives billing infrastructure choice.

hATTR amyloidosis is caused by pathogenic variants in the TTR gene producing misfolded transthyretin that deposits in nerves (PN phenotype) or heart (CM phenotype). The TTR-silencing class — siRNAs and antisense oligonucleotides (ASOs) — reduces hepatic TTR synthesis. Stabilizers like tafamidis bind TTR tetramer to prevent dissociation and are used primarily in cardiomyopathy.

Onpattro vs. Amvuttra — same target, very different billing FDA + Alnylam verified Apr 2026

Both are Alnylam siRNAs targeting TTR mRNA. Amvuttra has displaced most Onpattro use.

Alnylam's pipeline produced two siRNAs against TTR. Onpattro (2018) was the first — an LNP-encapsulated siRNA requiring IV infusion. Amvuttra (2022) is GalNAc-conjugated, allowing simple SC dosing every 3 months. Same molecular target; dramatically different patient experience and billing pathway.

Dosing & 0.1 mg unit math FDA label verified May 2026

Weight-based with a 30 mg flat cap at ≥100 kg. Multiply mg by 10 to get billable units.

Adult dosing

• <100 kg: 0.3 mg/kg IV every 3 weeks
• ≥100 kg: 30 mg flat dose IV every 3 weeks (NOT 0.3 mg/kg — weight-based formula caps)
• Lifelong therapy; no induction loading
• ~17 doses per year (q3wk × 52 weeks)

Unit conversion — the J0222 trap

J0222's HCPCS descriptor is "Injection, patisiran, 0.1 mg". Each billable unit equals 0.1 mg, not 1 mg. To compute units: multiply mg administered by 10. Most J-codes use a 1 mg unit basis — J0222 does not. This is the single most common biller error on Onpattro claims.

Worked example — 70 kg patient

Infusion timing — 80 minutes total

• Slow titration over the first 15 minutes (start at slow rate, escalate per label)
• Maintenance rate for the remaining ~65 minutes
• Total: ~80 minutes → bill 96365 (initial 1 hr) + 96366 (each addl hr) × 1
• Watch for infusion reactions throughout; document vitals and rate changes

NDC reference FDA NDC Directory verified May 2026

TTR genetic testing requirement FDA label + payer policies verified May 2026

A confirmed pathogenic TTR variant is required for the hATTR-PN indication.

Onpattro is approved for hereditary transthyretin-mediated amyloidosis with polyneuropathy. "Hereditary" is genotype-defined: a documented pathogenic variant in the TTR gene. Wild-type ATTR (ATTRwt, formerly senile systemic amyloidosis) is not on-label for Onpattro — only hereditary forms qualify.

Test coding

Vitamin A supplementation requirement FDA label verified May 2026

Patisiran reduces serum vitamin A by ~60%. Supplementation is a label-level requirement.

Transthyretin (TTR) is the primary serum carrier of retinol-binding protein (RBP), which transports vitamin A (retinol). Silencing TTR with patisiran reduces both circulating TTR and the RBP-retinol complex, dropping serum vitamin A by approximately 60% within the first dose. The FDA label requires oral vitamin A supplementation at the recommended daily allowance (RDA), approximately 2,500 IU/day, before and during therapy.

Documentation requirements

• Initiate vitamin A 2,500 IU/day PO before first Onpattro dose
• Document supplementation in the chart at every infusion visit
• Continue throughout therapy and into post-discontinuation period (until RBP/retinol normalize)
• Avoid high-dose vitamin A (> RDA) — toxicity risk in setting of low RBP transport
• Pregnancy category: avoid pregnancy on therapy due to vitamin A teratogenicity concerns and TTR-silencing effects

4-agent premedication protocol FDA label verified May 2026

All four agents required ~60 minutes before every Onpattro infusion. Mitigates ~19% infusion-reaction rate.

Onpattro infusion reactions occurred in approximately 19% of patients in clinical trials; most were mild to moderate. The label-mandated four-agent premedication regimen reduces incidence and severity. Skipping or substituting agents is a top denial trigger and a clinical safety risk.

Admin coding for premedication

• Each IV premedication agent can be billed as an additional therapeutic IV push or short infusion
• CPT 96374 (each additional IV push of a different drug) for sequential pushes; verify current AMA guidance
• If administered as concurrent infusions: 96367 (each additional sequential infusion of a different drug) may apply
• Document time given for each agent in the MAR — payers audit premedication for Onpattro claims

Administration codes CPT verified May 2026

Patisiran is non-chemo — therapeutic IV codes apply.

Modifiers CMS verified May 2026

JZ vs JW — weight-based dosing produces frequent waste

Effective July 1, 2023, CMS requires either JZ (no waste) or JW (waste reported) on every claim using a single-dose container. Onpattro's weight-based dosing with a fixed 10 mg vial size means most patients produce some partial-vial waste — JW is the more common modifier on J0222 claims. Patients at exactly 100 kg or above (30 mg flat cap = 3 full vials) and patients whose 0.3 mg/kg dose lands on a clean 10 mg multiple are the only no-waste scenarios — bill JZ.

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 infusion (e.g., neurology assessment for hATTR-PN progression). Routine pre-infusion clinical assessment is bundled.

340B modifiers (JG, TB)

For 340B-acquired Onpattro, follow your MAC's current 340B modifier policy. Alnylam's commercial billing guidance does not provide 340B-specific instructions.

ICD-10-CM FY2026 verified May 2026

Primary E85.1; supplementary G62.81 for the polyneuropathy phenotype.

Site of care & place of service Verified May 2026

Onpattro's 80-minute infusion plus ~60 minutes of premedication = ~2.5+ hours of chair time. Site steering is plan-specific, with most commercial payers preferring office and ambulatory infusion suites over hospital outpatient. Some plans approve home infusion via specialty home-infusion vendors familiar with the premedication protocol.

Claim form field mapping Alnylam Assist + payer guides 2026

From Alnylam Assist HCP coding & coverage materials.

Payer policy snapshot Reviewed May 2026

All major payers require specialist prescription, TTR variant documentation, neuropathy assessment, and premedication adherence.

Step therapy

With Amvuttra now on the market and offering substantially better convenience, some plans require step therapy through Amvuttra before approving Onpattro. Justification for IV over SC may include: Amvuttra intolerance, prior infusion-reaction history with vutrisiran, specific clinical preference for IV access, or patient preference (rarely sufficient alone). Verify per-payer at time of PA.

Reauthorization

Most plans reauthorize Onpattro every 6–12 months with documentation of clinical response (stable or improved neuropathy assessment, no progression). Some plans may flag patients still on Onpattro after Amvuttra became available and request switch justification at reauthorization.

Medicare reimbursement CMS Q2 2026 (live)

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

Coverage

No NCD specific to patisiran. Coverage falls under MAC LCDs for biologics + the generic drug-coverage framework. All MACs cover J0222 for FDA-approved on-label hATTR-PN with appropriate ICD-10, TTR variant documentation, and premedication / vitamin A documentation.

Code history

• J0222 — permanent code, "Injection, patisiran, 0.1 mg" (1 unit = 0.1 mg, NOT 1 mg)
• Pre-permanent-code period (2018–assignment): unclassified J3490 / J3590 with NDC documentation

Patient assistance — Alnylam Assist Alnylam verified May 2026

• Alnylam Assist: 1-833-256-2748 / alnylamassist.com — benefits investigation, prior authorization assistance, appeal support, copay program enrollment
• Onpattro Co-Pay Program: commercial copay support for eligible commercially-insured patients (excludes Medicare, Medicaid, federal program patients)
• Alnylam Patient Foundation: free product for uninsured / underinsured patients meeting income requirements
• Foundations for Medicare patients: refer to PAN, HealthWell, Patient Advocate Foundation — verify open hATTR / amyloidosis funds quarterly
• Sister product: Alnylam Assist also supports Amvuttra (J0225) through the same patient-services hub — transition support is integrated

Common denials & how to fix them

Frequently asked questions

What is the HCPCS code for Onpattro?

Onpattro (patisiran IV) is billed under HCPCS J0222 — "Injection, patisiran, 0.1 mg." Each billable unit equals 0.1 mg, NOT 1 mg. This is an unusual unit basis and a frequent biller error trap.

How many units do I bill for an Onpattro dose?

Multiply the mg administered by 10. For a 70 kg patient at 0.3 mg/kg = 21 mg = 210 units. For a patient ≥100 kg, the dose is capped at 30 mg = 300 units. Bill the administered units on one line and the discarded (wasted) units on a separate JW line.

What administration CPT do I use for Onpattro?

CPT 96365 (initial 1 hour therapeutic IV) plus 96366 (each additional hour). The 80-minute infusion runs ~20 minutes into the second hour, qualifying for one 96366 unit per most payer interpretations. Patisiran is non-chemo — do NOT bill 96413.

Is TTR genetic testing required before Onpattro?

Yes. Confirmed pathogenic TTR variant is required for the hATTR-PN indication. TTR gene full sequencing (CPT 81404) is the typical pre-treatment test. Document the specific variant in the chart and include the lab report with the PA submission.

Why is vitamin A supplementation required with Onpattro?

Patisiran reduces serum vitamin A (retinol) levels by ~60% by suppressing TTR, the carrier protein for retinol-binding protein (RBP). The FDA label requires oral vitamin A at the recommended daily allowance (~2,500 IU/day) before and during therapy.

What premedication is required before Onpattro?

All four agents, ~60 min before each infusion: (1) IV corticosteroid (dexamethasone 10 mg or methylprednisolone 500 mg); (2) oral acetaminophen 500 mg; (3) IV H1 (diphenhydramine 50 mg); (4) IV H2 (ranitidine or famotidine). The 4-agent regimen mitigates the ~19% infusion-reaction rate. Skipping or substituting agents is a top denial trigger.

What is the Medicare reimbursement for J0222?

For Q2 2026, J0222 reimburses at $100.896 per 0.1 mg unit (ASP + 6%) = $1,008.96 per mg. A 70 kg patient at 0.3 mg/kg dose (21 mg administered + 9 mg waste = 30 mg billable) reimburses at $30,268.80 per dose. Annualized (~17 doses/year): roughly $514,569/year. Sequestration (~2%) reduces actual paid to ~ASP + 4.3%.

How does Onpattro differ from Amvuttra?

Both are siRNA TTR-silencing therapies from Alnylam. Onpattro (J0222 patisiran) is IV every 3 weeks with required premedication + vitamin A + 80-min chair time. Amvuttra (J0225 vutrisiran) is a 1-mL SC injection every 3 months with no premedication required — now Alnylam's preferred product. Most patients have transitioned from Onpattro to Amvuttra. Onpattro is reserved for patients unable to tolerate or receive Amvuttra. See Amvuttra reference.

Source documents

1. Alnylam Assist — HCP coding & coverage materials
   Document footers: Alnylam Assist 2026; verified May 2026
2. DailyMed — ONPATTRO (patisiran) Prescribing Information
   FDA-approved label, most recent revision (BLA 210922)
3. FDA Onpattro original approval label PDF (2018)
4. CMS — Medicare Part B Drug ASP Pricing File
   Q2 2026 quarterly file, effective April 1 – June 30, 2026
5. FDA National Drug Code Directory — NDC 71336-1000-01
6. American Academy of Neurology — hATTR amyloidosis diagnosis & treatment guidelines
7. UnitedHealthcare — Medical drug coverage policy (patisiran)
8. Aetna — CPB on amyloidosis treatment
9. CareCost — Amvuttra (J0225) reference (sister siRNA, SC q3mo)
10. Alnylam Pharmaceuticals corporate — siRNA platform & pipeline

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 2026. FDA label: most recent revision (BLA 210922, original approval Aug 2018). hATTR landscape includes Amvuttra (J0225 SC q3mo, displaced most Onpattro use), Wainua (J1304 ASO SC q4wk), Tegsedi (J1306 limited use), tafamidis/acoramidis (oral, CM phenotype). Onpattro vs Amvuttra positioning emphasizes Amvuttra's adherence advantage.

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. The hATTR landscape is verified against current FDA labels for each agent. Premedication protocol and vitamin A supplementation requirements are quoted from the Onpattro FDA label. We do not paraphrase from billing-software vendor blogs.