The gate on anti-amyloid therapy is not price and not efficacy. It is amyloid confirmation and a coverage registry, and both are infrastructure problems.
A large population has Alzheimer's dementia and a larger one has mild cognitive impairment, but anti-amyloid therapy is confined to amyloid-confirmed disease at an early stage. Confirmation is the true gate. It was historically established by imaging or cerebrospinal fluid sampling, and more recently by a cleared blood-based test - a change that has more potential to move the treatable population than any competitive development, because it removes the capacity constraint that confirmation imposed.
Coverage compounds the infrastructure problem. Medicare pays only through a coverage-with-evidence-development registry, with confirmation and imaging-based safety monitoring required. A site that cannot meet the registry and monitoring obligations cannot treat, whatever a payer would otherwise reimburse. Access here is a question of site readiness rather than formulary position.
Between the approved agents, differentiation runs through burden rather than effect size. The reported difference in cognitive slowing is real but modest, and safety profiles are broadly comparable. In a therapy requiring infusion and repeated imaging over a long course, dosing interval determines chair throughput and patient burden, and does more competitive work than the efficacy delta. Both agents sit above independent value benchmarks and neither is yet exposed to Medicare negotiation.
AXLRx Alzheimer's reports run the funnel from prevalence through confirmation to the treatable pool, and read access as a site-infrastructure question.
Lecanemab versus donanemab in early AD. CMS amyloid-confirmation coverage and ARIA monitoring as the access gate.
US Alzheimer's staging, the amyloid-confirmation diagnostic pathway, and the FDA-cleared plasma pTau-217 blood test resizing the addressable pool.
CMS's coverage-with-evidence-development registry, not IRA negotiation, is the anti-amyloid access gate. ICER's below-value verdict and Part B routing set the rest.
Two anti-amyloid agents already sit inside CMS's coverage-with-evidence-development registry. A new entrant inherits that gate and must price inside ICER's benchmark to avoid Aduhelm's fate.
An estimated 7.2 million Americans aged 65 and over have Alzheimer's dementia, and 22% of seniors have mild cognitive impairment, but anti-amyloid therapy is confined to amyloid-confirmed MCI due to Alzheimer's disease and mild dementia. Amyloid confirmation is the true gate. It was historically established by PET or cerebrospinal fluid, and since May 2025 by an FDA-cleared plasma pTau217 and amyloid-beta-42 blood test. The size of the treatable population is set by confirmation capacity, and the blood test is the variable most likely to move it.
The registry, not the price. CMS covers lecanemab and donanemab under Medicare Part B only through Coverage with Evidence Development under national coverage determination 200.3, requiring amyloid confirmation and MRI monitoring for amyloid-related imaging abnormalities. A site that cannot meet the registry and monitoring requirements cannot treat, regardless of what a payer would pay. Infrastructure, not formulary position, is the binding constraint.
Less on efficacy than the headline numbers imply. Donanemab shows greater cognitive slowing at 35% against lecanemab's 27%, with similar rates of amyloid-related imaging abnormalities. But in a therapy requiring infusion and MRI monitoring, monthly dosing against bi-weekly is a meaningful access differentiator, because it determines infusion-chair throughput and patient burden across a long treatment course. The dosing interval is doing more competitive work than the cognitive delta.
Above the value benchmark and outside negotiation for now. ICER's April 2023 report found lecanemab priced above value, with a benchmark range of $8,900 to $21,500 against a $26,500 list price. Donanemab lists at roughly $32,000 a year with flexible-duration dosing, which changes the total cost of a course rather than the annual figure. Both are too recently approved for IRA negotiation and appear on no CMS selected-drug list for 2026 to 2028.
A patient-flow read that runs from prevalence through amyloid confirmation to the treatable pool, with confirmation capacity and the plasma test as the explicit levers; competitive intelligence on how the approved agents differentiate on dosing and monitoring burden rather than on effect size; and a payer analysis of the Coverage with Evidence Development registry, the site infrastructure it requires, and the ICER value gap. Each is scoped to your asset.