US Fabry Disease Patient Flow Model

Diagnosed classic Fabry disease in the US is estimated at 5,000-10,000 patients, roughly 1 in 40,000 males, per NORD and registry epidemiology. That figure describes the recognized population only. A later-onset, cardiac-predominant phenotype with residual enzyme activity is understood to be far more common but is largely undiagnosed, presenting in the fifth or sixth decade as isolated hypertrophic cardiomyopathy or chronic kidney disease rather than the childhood pain and angiokeratoma of classic disease. No current source in the AXLRx research base sizes that undiagnosed pool with a defensible number, so this funnel starts at diagnosis rather than inventing a total-prevalence estimate; closing that gap is a stated priority for the next model update, not a silent omission.

Within the diagnosed population, treatment eligibility splits on GLA-mutation amenability: 35-50% of patients carry a mutation the oral chaperone migalastat can stabilize, confirmed by a validated cell-based assay, per the FACETS and ATTRACT trials. That eligibility gate has been shifting the treated population's composition. Agalsidase beta (Fabrazyme) remains the dominant therapy at 60-65% market share after two decades with no direct US ERT competitor until 2023, but among newly treated, ERT-naive patients with a confirmed amenable mutation, 50-60% now start on oral migalastat, up from 40-50% choosing ERT as recently as 2020. The funnel therefore narrows twice after diagnosis: once on mutation amenability, and again on which mechanism a newly treated patient and physician actually choose.

Every AXLRx patient flow model is built on a five-layer funnel: population, disease burden (E1), diagnosis and capture (E2), treatment and mutation eligibility (E3), market access (E4), then Year 1-3-5 projections across three scenarios. Delivered as a live Excel workbook, not a static table: 104 formulas across 8 sheets, zero hardcoded cells.

This model begins at the diagnosed population because no source in the current research base sizes total or undiagnosed US Fabry prevalence with a defensible figure; NORD and registry sources describe the recognized classic-Fabry population only. Sizing the undiagnosed, largely cardiac-predominant later-onset pool is a known gap, flagged here for a future model update rather than filled with an invented number. Sources: NORD / Fabry registry epidemiology, FACETS (NEJM 2016), ATTRACT (J Med Genet 2017), Fabry Registry US patient cohort, and Amicus investor day 2024.