ARIA monitoring infrastructure is the rate-limit on anti-amyloid uptake

Signal

Two years into the lecanemab rollout and eighteen months into donanemab, the practical constraint on real-world uptake is not clinical demand or payer authorisation but the MRI surveillance protocol both products require. Lecanemab's FDA label calls for MRI before infusions 5, 7 and 14 (and earlier if symptoms suggest ARIA), and donanemab's label calls for MRI before infusions 2, 3, 4 and 7. Combined with baseline imaging and APOE genotyping prior to treatment initiation, the per-patient imaging burden is substantially higher than any prior chronic neurology therapy on the US market.

Multiple major academic centres - Mayo Clinic, Cleveland Clinic, Mass General Brigham, Washington University in St Louis - have published or presented data through 2025 and early 2026 reporting that the throughput limit at their infusion-and-imaging programmes is in the low hundreds of patients per centre per year. The constraint is not the infusion chair (1-hour appointments, scalable) but the surveillance MRI slot (60-90 minute appointments, scarce). Patients in lower-resource markets face waitlists measured in months for a baseline MRI before they can even start.

Why it matters

For commercial teams at Eisai/Biogen and Eli Lilly, the implication is that demand-side marketing has limited near-term return. The constraint is downstream of the prescribing decision and downstream of the payer decision. Marginal capacity unlocks come from: subcutaneous formulations that reduce infusion-chair time, lower-burden surveillance protocols (an active discussion at FDA), and any successful argument for risk-stratified MRI cadence (fewer scans for non-APOE4 patients).

For payers, the implication runs the other direction: the same infrastructure constraint that frustrates manufacturers is the de facto utilisation cap for the line. Coverage decisions can be relatively permissive on the prescribing criteria because the infrastructure ceiling enforces a smaller real-world denominator than headline approval might suggest.

What we are watching

• Lecanemab subcutaneous (Leqembi IQLIK) - Eisai filed the supplemental BLA in Q1 2025; approval would shift weekly self-administration from infusion-chair time to home use, easing the chair-side bottleneck but not the MRI bottleneck.
• Donanemab subcutaneous - Lilly has signalled development; no public dose-finding readout as of mid-2026.
• FDA dialogue with the AAN on whether the post-treatment MRI cadence can be reduced for low-risk genotypes. Real-world ARIA-E rates in non-APOE4 carriers are well below the trial population's pooled rate, supporting an argument for fewer surveillance scans in that subgroup.
• CMS coverage decisions in 2026-27 on whether reimbursement for the imaging cadence keeps pace with prescribing volume. Underpaid imaging gets deprioritised against higher-margin scans on the same MRI scanner.