Key takeaways
- 15–20K estimated US PNH prevalence across three phenotypes (International PNH Registry; disease-landscape analysis)
- ~3,500 US patients on complement-inhibitor therapy today (~55% ravulizumab, ~25% eculizumab, ~10% iptacopan)
- 800–1,200 treated patients with extravascular haemolysis (EVH), persistent anaemia despite anti-C5 blockade
- 2.4 years mean diagnostic delay from first haemolytic symptom to confirmed PNH diagnosis (International PNH Registry)
15,000 to 20,000 Americans carry a PNH clone. Only about 3,500 reach complement-inhibitor therapy, and up to 1,200 of them remain anemic on it, the gap this model has to size precisely.
The funnel narrows in stages that a single prevalence number hides. An estimated 15,000 to 20,000 US patients carry a PNH clone large enough to be clinically significant, split across three distinct phenotypes: haemolysis-dominant disease (8,000 to 10,000 patients), aplasia-dominant disease with a hypocellular marrow (4,000 to 5,000), and thrombotic PNH presenting at unusual vascular sites (2,000 to 3,000). Mean diagnostic delay runs 2.4 years from first haemolytic symptom to confirmed diagnosis, per the International PNH Registry, because early symptoms mimic autoimmune haemolytic anaemia, aplastic anaemia, or MDS. Roughly 500 to 700 new patients are diagnosed each year, and an estimated 200 to 400 patients annually go undertreated at hospitals without PNH specialist capacity.
Of the diagnosed population, approximately 3,500 US patients are on complement-inhibitor therapy today: about 55 percent on ravulizumab, 25 percent on eculizumab, and roughly 10 percent already switched to iptacopan within six months of its November 2023 launch. That treated population is not the end of the funnel. Between 800 and 1,200 of them have extravascular haemolysis (EVH), persistent anaemia despite adequate C5 blockade, and a narrower subset of 600 to 900 transfuse at least once a year despite treatment. That EVH-transfusing cohort, not the full prevalence estimate, is the population any proximal-complement or novel-mechanism asset actually has to reach.
US PNH funnel — from clonal prevalence to the EVH-persistent-anaemia pool
| Funnel Stage | Population | Source |
|---|---|---|
| Estimated US PNH clonal prevalence | 15,000–20,000 | International PNH Registry-based disease-landscape analysis |
| Diagnosed and on complement-inhibitor therapy | ~3,500 | Published US PNH treatment-share analysis |
| Persistent anaemia despite anti-C5 blockade (EVH) | 800–1,200 | APPLY-PNH trial screening population |
| Transfusion-dependent EVH subset (label-relevant) | 600–900 | APPLY-PNH trial inclusion criteria |
Sources: International PNH Registry; published US PNH treatment-share and EVH-prevalence analysis; APPLY-PNH trial (NEJM 2023); AXLRx disease-landscape and launch-readiness research.
What this model answers
Every section answers a named commercial question your team is asking, scoped to your asset.
- How many US patients actually sit in the treated, EVH-persistent-anaemia pool, versus the full 15,000-to-20,000 prevalence estimate? • The three-phenotype prevalence split • the ~3,500-patient treated population and its agent-share breakdown • the narrower 600-to-900-patient transfusion-dependent EVH cohort a differentiated asset must target
- Where does the funnel leak between clone and treatment, and how large is the undertreated population? • The 2.4-year mean diagnostic delay and its differential-diagnosis causes • 500-to-700 annual new diagnoses • the 200-to-400-patient annual undertreated population at non-PNH-centre hospitals
- What does the live, re-runnable funnel model actually contain, and how is every conversion step sourced? • 8-sheet structure mirroring the standard AXLRx patient flow architecture • source citation to the International PNH Registry, APPLY-PNH trial data, and published disease-landscape analysis per conversion step
What's inside
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1 · The Binding Constraint 2 pp
- Why the EVH-transfusing subset, not total prevalence, sets the addressable pool
- Pressure-tested against the treated-population agent split before the rest of the model is built out
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2 · Disease Burden (E1) — Clonal Prevalence 3 pp
- 15,000-20,000 US PNH prevalence across three phenotypes
- Haemolysis-dominant, aplasia-dominant, and thrombotic PNH sized separately
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3 · Diagnosis & Capture (E2) — Treated Population 4 pp
- ~3,500 patients on complement-inhibitor therapy; 2.4-year mean diagnostic delay
- 500-700 annual new diagnoses and the 200-400-patient annual undertreated pool
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4 · Residual Disease Eligibility (E3) — EVH Segment 3 pp
- 800-1,200 patients with persistent anaemia despite anti-C5 blockade
- Narrowing to the 600-900-patient transfusion-dependent, label-relevant cohort
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5 · Market Access (E4) — Payer Routing 3 pp
- Medicare Part B (IV incumbents) versus Part D (oral agents) routing differential
- PBM prior-authorisation criteria forming around FLAER clone size and LDH thresholds
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6 · Sensitivity Analysis 3 pp
- Which assumption moves the eligible pool most: diagnostic delay or EVH share
- Scenario ranges across the three phenotype segments
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7 · Year 1·3·5 Projections 4 pp
- Patient volume by horizon under conservative, base, and aggressive uptake scenarios
- Revenue translation inputs
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8 · Client Alignment Questions 2 pp
- The open questions your forecasting team must close before the model is finalised
- Structured for an internal forecast-review session
Appendix and source ledger included · 45-minute analyst readout included with delivery
Custom model delivered in 72 hours.
Assess this reportIncluded with every brief
Get Started
Commission this model
AXLRx delivers rare disease patient flow models built for forecasting and launch teams sizing the US PNH opportunity. Custom model in 72 hours.
- 1. Submit your requestSpecify your indication, market, and cohort definition.
- 2. Scoping callAXLRx analyst confirms funnel scope and comparator set before building.
- 3. DeliveryResearch-verified patient flow model in 72 hours with optional analyst readout.
How AXLRx builds this model
Prepared by MoatRx analysts on the AXLRx commercial consulting engine.
Every AXLRx patient flow model is built on a five-layer funnel: population, disease burden (E1), diagnosis and specialist capture (E2), treatment and biomarker eligibility (E3), market access (E4), then Year 1-3-5 projections across three scenarios. Delivered as a live Excel workbook, not a static table: 112 formulas across 8 sheets, zero hardcoded cells.
US PNH sources: International PNH Registry diagnostic-delay data, published US treatment-share and phenotype-prevalence analysis, and APPLY-PNH trial (NEJM 2023) EVH-response and inclusion criteria.
- US PNH clonal prevalence and phenotype split verified against International PNH Registry-based disease-landscape analysis
- Treated-population size and agent-share breakdown verified against published US PNH treatment-share analysis
- EVH prevalence and transfusion-dependent subset verified against APPLY-PNH trial (NEJM 2023) screening and inclusion data
- Diagnostic delay and annual new-diagnosis estimate verified against International PNH Registry publications
Frequently asked questions
Deliverables What formats are included with every model?
Every commissioned Patient Flow Model includes an editable 8-sheet Excel funnel model (Strategic Context, Inputs, Model, Projections, Sensitivity, References, Market Context, QC), a PDF methodology brief, and an optional executive readout deck for forecasting and launch team presentations. A 45-minute analyst readout call is included.
Sources How is the epidemiology evidence verified?
AXLRx builds from primary sources only, the International PNH Registry, APPLY-PNH trial data, and published treatment-share analyses, not secondary market research summaries. Every conversion rate is cited to a primary source and re-runnable in the model.
Customisation Can I tailor the cohort definition or comparator set?
Yes. The intake form captures your indication, target market, cohort definition, and comparators. A scoping call confirms scope before research starts. Commission via the intake form to start.