US PNH Pricing Strategy Model

The Inflation Reduction Act created Medicare drug price negotiation, but the orphan-drug exclusion removes an entire class from its reach. A drug qualifies for the exclusion if it carries only orphan-designated indications and no non-orphan indication; the 2025 One Big Beautiful Bill Act broadened that definition, and it captures the full anti-C5 franchise, PNH, atypical HUS, generalized myasthenia gravis, and neuromyelitis optica spectrum disorder, for both ravulizumab (Ultomiris) and eculizumab (Soliris). Neither drug appears on any CMS Medicare Drug Price Negotiation Program selected-drug list published to date (IPAY 2026, 2027, or 2028). Eculizumab carries a second structural bar: FDA-approved interchangeable biosimilars, Bkemv and Epysqli, both cleared in 2024, which affect its negotiation-eligibility calculus independently of the orphan exclusion. The result is a price anchor that does not reset the way it would for a non-orphan biologic at the same revenue scale.

Absent a negotiated ceiling, ICER's advisory cost-effectiveness assessment is the closest thing the US market has to a formal value benchmark, and it is not favorable to the newest entrant. ICER's March 2024 evidence report on iptacopan versus C5 inhibitors in EVH-experienced PNH patients rated the drug Promising but Inconclusive and set a health-benefit price benchmark of $156,000 to $157,000 annually, against iptacopan's own approximately $550,000 WAC, a gap that implies roughly a 71% discount before the drug would clear ICER's own cost-effectiveness bar. Benefit routing compounds the pricing problem: Ultomiris, Soliris, and Piasky are administered products that route through Medicare Part B, where dual-eligible beneficiaries carry no copay, while Fabhalta, an oral agent, routes through Part D, exposing beneficiaries to the redesigned benefit's annual out-of-pocket cap instead. No major commercial payer, UnitedHealthcare, CVS/Aetna, Cigna, Anthem, or Humana, had published a formal IV-to-oral switch protocol as of mid-2024; each anchors prior authorization on an LDH threshold of at least 1.5 times the upper limit of normal plus a FLAER clone of 10% or more. Our price ladder models what a new entrant would need to concede against the ICER benchmark, and where Part B versus Part D routing changes the practical net price a payer will actually accept.

Every AXLRx pricing model is built from primary regulatory and HTA sources, FDA, CMS, and ICER evidence reports, not secondary summaries. Findings are independently verified before inclusion.

PNH US pricing sources: ICER PNH Evidence Report (Iptacopan and Danicopan), March 13, 2024; CMS Medicare Drug Price Negotiation Program selected-drug lists (IPAY 2026-2028) and OBBBA orphan-exclusion guidance; FDA Drugs@FDA; FDA biosimilar approvals (Bkemv, Epysqli); major US commercial payer PA policy documents (UHC, CVS/Aetna, Cigna, Anthem, Humana).