US ATTR Amyloidosis Pricing Analysis: Four Agents, Two Benefit Rails, One Orphan-Drug Shield

US ATTR amyloidosis therapy divides into two mechanistic camps priced very differently. The oral TTR stabilizers anchor the lower band: Pfizer's tafamidis (Vyndamax 61mg, one capsule daily; the lower-dose Vyndaqel 20mg meglumine capsule is now marked Discontinued in Drugs@FDA and is being wound down in the US) carries a list price of roughly $268,000 per year as of 2024-2025, up from the $225,000 at its May 2019 US launch (source: Pfizer disclosures via TCTMD / BioPharma Dive; launch price confirmed in Kazi et al., Circulation 2020, PMID 32078382).

BridgeBio's acoramidis (Attruby), FDA-approved November 22, 2024 for ATTR-CM, launched at $18,759 per 28-day supply — approximately $244,000 per year — deliberately undercutting tafamidis by roughly 9% on list (source: BridgeBio / FiercePharma / BioPharma Dive, company disclosure).

The RNA-silencing camp sits far higher. Alnylam's vutrisiran (Amvuttra), approved for ATTR-CM in March 2025, is priced at about $476,000 per year (quarterly subcutaneous dosing, ~$119,000 per dose); patisiran (Onpattro), the earlier IV RNAi agent, carries a WAC near $477,000 per year but is approved only for hereditary ATTR polyneuropathy, not the cardiomyopathy indication (source: BioPharma Dive, Cardiac Wire, company disclosure). The list-price spread across the class therefore runs from ~$244K to ~$477K — roughly a 2x gap driven entirely by modality and benefit routing, not by outcomes.

The commercially decisive event is not a price level but a price rivalry. Before November 2024, tafamidis was the only oral stabilizer and negotiated from monopoly. Acoramidis' entry created the first head-to-head stabilizer contest on the same Part D formulary tier for the same ATTR-CM patient. Acoramidis launched below tafamidis on list precisely to give pharmacy benefit managers a credible second option.

That converts list price into rebate leverage. With two clinically substitutable oral stabilizers competing for preferred placement, PBMs and Part D plans can extract deeper rebates than either sponsor conceded in the monopoly era, pushing net prices materially below the ~$244K-$268K WAC band (the precise net-to-WAC erosion is tracked by SSR Health from Medicaid rebate data but is not publicly disclosed at the brand level — flagged as a data gap rather than estimated here). The strategic read: WAC is now a negotiating anchor, and the real ATTR-CM stabilizer price is set in the rebate, not the list.

The stabilizer economics are further pressured from below. Pfizer reached multiple settlement agreements with generic tafamidis filers across 2025-2026, signaling generic entry on the horizon ahead of the compound's patent expiry — a second source of net-price compression distinct from the acoramidis rivalry (source: Pfizer / BusinessWire, FiercePharma).

Benefit routing is a first-order pricing variable in US ATTR, not an administrative footnote. The oral stabilizers (tafamidis, acoramidis) are self-administered and adjudicate through Medicare Part D, the pharmacy benefit — where the IRA's redesign now caps beneficiary out-of-pocket spending at $2,000 per year (2025 onward), sharply lowering the patient-facing cost of a $250K drug and, per IQVIA commentary, supporting stabilizer volume growth.

The RNAi silencers route through Medicare Part B, the medical benefit: patisiran by IV infusion and vutrisiran by provider-administered subcutaneous injection are billed buy-and-bill under HCPCS J-codes at ASP plus 6%. Part B carries 20% coinsurance without the Part D out-of-pocket cap unless the patient holds supplemental coverage — so the ~$476K silencers can expose beneficiaries to far larger cost-sharing than the higher-volume oral stabilizers. The same disease, the same payer, two entirely different access economics depending on molecule format (source: CMS Part B/Part D program structure; Aetna / MO HealthNet coverage bulletins for J-code routing).

A correction to a common assumption is warranted here: tafamidis has NOT been selected for Medicare drug price negotiation in any of the program's three cycles. It is absent from the initial 10 drugs for IPAY 2026 (effective January 1, 2026), from the 15 drugs for IPAY 2027 (effective January 1, 2027), and from the 15 drugs for IPAY 2028 announced January 27, 2026 (effective January 1, 2028) — the first cycle to include Part B drugs (source: CMS selected-drug fact sheets; AMCP, Ritter Insurance Marketing summaries).

The reason is structural. Tafamidis holds orphan designation for transthyretin amyloidosis and no non-orphan indication. Under the IRA's orphan-drug exclusion — expanded by the One Big Beautiful Bill Act signed July 4, 2025 to protect drugs with one or more orphan designations and to restart the negotiation-eligibility clock from a drug's first non-orphan approval — a multi-orphan-designation product like tafamidis remains outside the negotiation-eligible pool (source: Sidley Austin, Morgan Lewis legal analyses; NORD). Acoramidis and the silencers, all orphan ATTR agents, sit behind the same shield. The practical consequence: in the US, ATTR pricing discipline will come from competition, rebates, and eventual generics — not from CMS-negotiated Maximum Fair Prices.

Independent value assessment has been consistent and stark. According to PubMed, Kazi et al. (Circulation, 2020, PMID 32078382) modeled tafamidis at an incremental cost-effectiveness ratio of $880,000 per QALY at its then-$225,000 list price, and found a 92.6% price cut — to roughly $16,563 per year — would be required to reach a $100,000/QALY threshold ([DOI](https://doi.org/10.1161/CIRCULATIONAHA.119.045093)).

The formal HTA followed in October 2024: ICER's final evidence report on ATTR-CM set a health-benefit price benchmark of $13,600 to $39,000 per year for the TTR stabilizers tafamidis and acoramidis, implying an 85% to 95% discount from the ~$268,000 tafamidis list price to reach a $100,000-$150,000/QALY value range (source: ICER final report, October 2024). Whichever benchmark is used, the US list prices sit roughly an order of magnitude above assessed value — a gap that, absent IRA leverage, only market competition and net-price rebating can close.

This sub-page corrects two premises worth flagging for the parent Payer & HTA report: (1) tafamidis is not an IRA-negotiated drug and has no Maximum Fair Price effective 2026 — it is orphan-exempt; (2) the authoritative ICER ATTR-CM assessment is dated 2024, with the earlier value benchmark coming from the 2020 Kazi Circulation analysis.