Lecanemab Planning

Abstract

Background

Approximately 6.9 million American individuals have Alzheimer dementia and 50% have mild disease. Lecanemab, an approved antiamyloid antibody, is associated with modest reduction in functional decline in patients with mild dementia or mild cognitive impairment. In Clarity-AD, 239 (26.6%) of patients experienced amyloid-related imaging abnormalities (ARIAs) overall (i.e., ARIAs associated with hemorrhages or edema). The complexity of treatment and risks of adverse events necessitate a multidisciplinary collaborative approach.

Recent Findings

With limited treatment options, lecanemab approval generated significant interest among clinicians, patients, and families. Lecanemab treatment requires biweekly infusions along with ongoing imaging tests, laboratory monitoring, patient assessment, drug interaction screening, and cognitive function monitoring. Processes to support patient selection, access, and safety are important given the monitoring requirements and total cost of care.

Implications for Practice

The planning process for lecanemab can serve as a blueprint to support safe and effective management of therapeutic innovation in neurology and other areas.

Introduction

The US Food and Drug Administration (FDA) recently approved lecanemab for the treatment of Alzheimer disease in patients with mild cognitive impairment or mild dementia.¹ In clinical trials, lecanemab modestly reduced the rate of disease progression and slowed cognitive and functional decline at 18 months of therapy.² Lecanemab is administered as a biweekly infusion. Criteria for discontinuation include progression to moderate dementia or serious adverse reactions. The most common adverse events reported are infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (ARIAs), which include ARIA with cerebral microhemorrhages or hemosiderin deposits (ARIA-H) (14%) and ARIA with edema and effusion (ARIA-E) (12.6%); seizures have also been reported.² People taking concomitant anticoagulants and lecanemab were found to have a higher incidence of intracranial hemorrhage compared with those on placebo.³ Thus, periodic MRI monitoring and patient assessment, including a thorough medication history evaluation before each infusion, are essential to ensure safe use.⁴ As a result, the total cost of treatment significantly exceeds the cost of the medication alone.

Multidisciplinary Committee: Engaging Stakeholders to Support Access and Safety

Given the prevalence of mild disease and anticipated high demand for new Alzheimer treatment options, health systems are faced with challenges on how to support the complexity of lecanemab management. Our institution began planning for amyloid beta-targeting antibody treatment almost a year before the full FDA approval of lecanemab in July 2023. A multidisciplinary committee established as a subcommittee of the Pharmacy and Therapeutics Committee initially focused on aducanumab and pivoted to lecanemab based on published trial results released in November 2022 and evidence that the adverse event profile and payer coverage would be barriers to use of the former. The goal of the multidisciplinary subcommittee, with broad representation from neurology, geriatrics, neuroradiology, neuropsychology, emergency department, stroke team, pharmacy, bioethics, and risk management, was to create a blueprint for safe use and access. Leadership representation also included the following departments: finance, managed care contracting, and office of health equity. Monthly meetings facilitated by pharmacy supported planning and decision making and development of implementation tools and tactics.

Implementation Tools and Tactics

• A comprehensive orderset was developed based on the pivotal trial clinical criteria, payer policies, and input from the committee to guide physicians in patient selection and reduce the risk of harm associated with lecanemab infusions. Exclusion criteria, cognitive and functional test scores, bleeding risk factors, and monitoring requirements were built into the orderset. Given the risk of ARIA-H, the committee recommended a requirement for a biweekly medication history assessment to determine whether anticoagulants or over-the-counter products, including herbal supplements known to increase bleeding risk, had been initiated since the previous dose. A lecanemab attestation was included which requires the physician to provide the medication guide and discuss potential risks and benefits and alternatives with the patient and the patient's designated adult surrogate as described below. The orderset supports an objective approach to patient selection and serves as an educational guideline for prescribers and the care team.

• A consent form was developed with the guidance of risk management that provides information on the risks of ARIAs and includes the designation of a designated adult surrogate (e.g., family members, significant other, etc.) who would support the patient and make medical decisions should the patient no longer have the capacity to make them as determined by the treatment team.

• Guidelines for emergency management of patients on lecanemab, presenting with ARIA-like symptoms were developed and shared with the health system emergency departments and urgent care centers. In addition, because patients on lecanemab can present with sudden neurologic deterioration consistent with a stroke, neurocritical care and stroke team clinicians were engaged in the guideline development process.

• The total cost of care for lecanemab treatment per patient per year was calculated to inform clinicians and executive leadership and guide equitable decision making. This was important to support patient access for patients who meet clinical criteria and for whom the benefit outweighs the risk. A process for financial counseling was developed to support patient access. We tabulated the institution-specific costs for treatment and monitoring including drug acquisition and administration costs and laboratory, imaging, cognitive, and functional tests. Physician, pharmacist, and support staff costs were not included in the calculation because it was assumed that physicians would bill for encounters and the pharmacist and support staff costs are not readily quantifiable.

Strategic Planning: Pilot Program and Prospective Clinical Panel Reviews

Based on the need for extensive care coordination for lecanemab biweekly infusions, a pilot was proposed to gain experience with patient selection and monitoring. The pilot would be limited to 10 patients and 5 designated prescribers, appointed by the Neurology Department. To support access to treatment, physicians whose patients meet eligibility criteria as delineated in the orderset would be able to refer these patients to one of the designated prescribers as outlined in Figure 1. The proposal included establishing a prospective clinical review panel based on positive previous experiences with this model for managing decision making during the COVID-19 pandemic and for other complex therapies. This pilot was designed to support safe use, access, and shared learning and was approved by a newly established Therapeutic Innovation Stewardship Committee, the Neurology Department, Finance and the Pharmacy and Therapeutics Committee.

Figure 1. Lecanemab Ordering.

Flowchart of process for ordering lecanemab with clinical review panel. DP = designated prescriber who can order lecanemab; RP = referring provider who can send referrals for any patients deemed eligible based on criteria outlined in the orderset; RX = pharmacy.

The clinical review panel includes 2 of the designated prescribers, a neuropsychologist and 1 physician representative each from the Pharmacy and Therapeutics (P&T) and Bioethics Committees. The panel is coordinated by Pharmacy leadership and convenes periodically to review cases based on receipt of completed ordersets. During the panel review, one of the designated prescribers, who is not serving as a reviewer, presents a clinical synopsis of the case, and the panel reviews the MRI, cognitive and functional test results, laboratory test results, and patient\family\caregiver support for treatment. The panel may request additional information, such as a more recent cognitive test, to make the determination of whether to proceed with initiation of treatment. Because the panel review process is based on objective parameters applied to a clinical case, the discussion generally consists of clarifying questions and decisions to proceed with therapy have been consistently consensus-based without opposition.

Blueprint for Safe and Effective Management of Lecanemab

The following elements represent the lecanemab blueprint developed by the multidisciplinary subcommittee referenced above:

• Comprehensive informed consent process that includes provision for an authorized surrogate when adult patients lack the cognitive ability to complete the biweekly assessments and manage their infusions and diagnostic tests.

• Detailed orderset that integrate required laboratory test results, imaging, cognitive and functional tests, and other screenings for initiating and continuing therapies.

• Emergency department and urgent care center management protocols for identifying and managing ARIA or acute care conditions requiring initiation of an antithrombotic and/or thrombolytic agent, as outlined in Figure 2.

• Leveraging technology to inform the health care team of severe drug-drug interaction when an antithrombotic or thrombolytic agent is ordered for patients on lecanemab or have received lecanemab in the previous 1-month timeframe.

• Biweekly patient assessment and patient's authorized surrogate for changes in condition, medications or adverse events via secure messaging and outreach and documentation of lecanemab therapy in the electronic medical record (EMR) throughout the treatment course, as outlined in Figure 3.

• Financial authorization and support for under or uninsured patients.

• Scheduling of baseline, periodic imaging, and biweekly infusion appointments.

• Monthly follow-up phone calls and quarterly in-person clinic visit with the treating physician.

• Educational program for health care providers (medical staff, neurology, emergency department, urgent care, imaging, pharmacy, and nursing) to ensure timely identification and management of infusion-related reactions and ARIA.

• Physician review panel case reviews to support patient safety, access, and consistency in treatment decisions.

Figure 2. ED and Urgent Care Management of Patients on Lecanemab.

Flowchart for process of managing patients taking lecanemab in the ED and urgent care. ARIA = amyloid-related imaging abnormalities with signs and symptoms including headaches, altered mentation, dizziness, seizures, etc.; DP = designated prescriber who can order lecanemab.

Figure 3. Lecanemab Therapy Monitoring.

Flowchart for process of monitoring patients on lecanemab therapy, including preinfusion and postinfusion communication to patients/designated adult surrogate for medication changes and potential adverse drug reactions. DP = designated prescriber who can order lecanemab.

On the completion of the pilot, the Pharmacy plans to conduct a postpilot survey to obtain feedback from the clinician review panel, Committee members, and participating medical staff. In addition, the Committee will determine next steps with respect to place in therapy for lecanemab, including the subcutaneous dosage form, and donanemab since FDA approval of the latter 2 therapies are anticipated this year.

Conclusion: The Path Forward

Between January 2022 and February 2024, 94 novel therapies were approved by the FDA to provide new treatment options for patients and advances in health care with an additional 30 anticipated this year.^5,6 The accelerated availability, high cost, and safety considerations associated with these breakthroughs, which often require close initial and longitudinal monitoring and, in some cases, hospitalization, create challenges for patients, providers, and health systems. The experience gained through this comprehensive multidisciplinary planning process has provided a blueprint for the management of lecanemab and forms the foundation for supporting patient safety and ensuring access to future novel therapies.

TAKE-HOME POINTS

• → With the increasing FDA approval of high-cost therapeutic innovation, a comprehensive multidisciplinary planning process supports objective patient selection, access, and safety.

• → Implementation of a panel review process creates an equitable decision-making process by enabling clinicians to integrate evidence, expertise, safety, ethics, and equity in patient selection for treatment.

• → The complexity associated with emerging new biologics and cellular and gene therapies necessitates a methodology for determining the total cost of care to support organizations in determining which therapies will be made available.

• → Risk management, bioethics, and patient financial services play key roles in the multidisciplinary planning process for breakthrough therapies.

• → Developing a process to monitor positive pivotal trials and begin the planning process for breakthrough therapies is important to support patient access once the therapies are approved.

Appendix. Authors

Name	Location	Contribution
Rita Shane, PharmD	Department of Pharmacy Services, Cedars-Sinai Medical Center	Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data
Sarah Kremen, MD	Department of Neurology, Cedars-Sinai Medical Center	Drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data
Zaldy S. Tan, MD, MPH	Department of Neurology, Cedars-Sinai Medical Center	Drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data
Hai Tran, PharmD	Department of Pharmacy Services, Cedars-Sinai Medical Center	Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data
Thanh G. Tu, PharmD	Department of Pharmacy Services, City of Hope, Los Angeles, CA	Drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data
Nancy L. Sicotte, MD	Department of Neurology, Cedars-Sinai Medical Center	Study concept or design

Study Funding

The authors report no targeted funding.

Disclosure

S. Kremen was a consultant for Eli Lilly and Company relating to donanemab. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.