How do step therapy protocols apply to newly approved Alzheimer's drugs?
Executive summary
Step-therapy protocols are insurance tools that require patients to try and fail cheaper or older treatments before accessing newer anti-amyloid Alzheimer’s drugs such as lecanemab and donanemab; clinical and policy literature in 2025 shows these monoclonal antibodies target early-stage disease and are being incorporated into new care pathways but raise access, equity and implementation questions [1] [2] [3]. Health systems and specialty clinics are creating rigorous eligibility protocols and biomarker-driven pathways to identify appropriate patients, while national guidelines and evidence reviews are updating testing and use criteria to support that process [3] [4] [5].
1. What step therapy means for Alzheimer’s in 2025 — a gatekeeper, not a treatment decision
Step therapy is an insurer-driven sequence that requires failure on certain prior options before covering a newer agent. In the case of Alzheimer’s, that often translates into mandating trials of symptomatic drugs or non-drug interventions and objective biomarker confirmation before payers will approve high-cost anti-amyloid immunotherapies — a dynamic that shifts the clinical debate about “who gets treated first” from clinicians to benefits managers (available sources do not mention specific payer step policies; sources describe the arrival and intended use of the new monoclonals) [1] [2]. The literature emphasizes that the monoclonal antibodies lecanemab and donanemab were approved for early-stage disease and depend on biomarker-defined eligibility, which insurers can use as a formal step to restrict access [1].
2. Why biomarker-driven eligibility fuels step requirements
Regulators and guideline bodies have tied the approved use of anti-amyloid antibodies to objective evidence of amyloid pathology. Updated appropriate-use criteria and clinical practice guidelines now explicitly recommend amyloid testing (including imaging and blood-based biomarkers) both to determine eligibility and to monitor response — creating natural checkpoints insurers can incorporate into step pathways before authorizing therapy [4] [5]. Clinical reviews and health systems report that care teams are building “rigorous protocols” to identify eligible patients, underscoring that biomarker confirmation is treated as a prerequisite to therapy delivery [3].
3. Health systems respond with standardized care pathways
Leading memory clinics and academic programs have designed rigorous protocols to operationalize patient selection, safety monitoring and long-term follow up for disease-modifying therapies. Those institutional pathways mirror, and sometimes predate, insurer step rules — meaning that even where payers are permissive, practical access remains controlled by clinical eligibility criteria and resource constraints [3]. This creates a two-tiered reality: clinical gatekeeping based on science and administrative gatekeeping based on cost and coverage.
4. Cost, capacity and equity shape how step therapy plays out
Anti-amyloid antibodies are expensive and require infrastructure (infusions, imaging, safety surveillance) that amplifies insurers’ incentives to impose steps. The World Dementia Council and implementation reports warn of unresolved issues around global equity and access as therapies scale up; they also document that clinics are already prioritizing who is treated first based on eligibility algorithms — a process step therapy can formalize at the benefit level [3]. The combination of price, required diagnostics and center capacity means step rules are likely to disproportionally affect underserved communities unless explicitly countered by policy [3].
5. Competing perspectives in the reporting
Clinical investigators and specialist centers argue that rigorous selection and biomarker confirmation protect patients and maximize benefit from these therapies [3] [4]. Payer advocates and budget-conscious stakeholders stress that step therapy preserves sustainability and ensures cheaper or established approaches are tried first (available sources do not quote payer spokespeople directly). Patient advocates worry such steps will delay access to disease-modifying care for those most likely to benefit (available sources do not provide direct patient-advocate quotes on step protocols); the reporting indicates a tension between ensuring appropriate use and preventing undue barriers.
6. Practical implications for clinicians and patients
Clinicians must now document biomarker status, disease stage and prior therapeutic trials to navigate coverage. Health systems are already creating standardized pathways that clinicians will need to follow to get therapies approved and safely delivered [3] [4]. The evolving clinical guidance and evidence syntheses published in 2025 — which endorse early-stage intervention informed by biomarkers — will be the main lever clinicians use to contest restrictive step decisions when appropriate [1] [5].
7. What’s missing and what to watch
Current reporting lays out where the drugs fit clinically and how systems are organizing delivery, but available sources do not catalog specific insurer step-therapy policies, nor do they provide systematic data on how often payers deny or delay access through step requirements (available sources do not mention detailed payer policy inventories or denial rates). Watch for forthcoming payer coverage rules, state-level mandates, and guideline updates that will determine whether step therapy becomes a temporary triage tool or a long-term barrier to these new Alzheimer’s treatments [5] [4].
Limitations: this analysis draws solely on 2025 clinical reviews, pipeline reports and implementation dialogues that describe drug approvals, biomarker guidance and health-system protocols; direct empirical study of payer step policies and denial patterns was not available in the provided sources [1] [2] [3] [4] [5].