Anti-amyloid Therapy

DIAD CLINIC

Cognitive Neurology Unit’s Disease Modifying Immunotherapies for the treatment of Alzheimer’s Disease (DiAD) clinic

ANTI-AMYLOID MONOCLONAL ANTIBODY INFORMATION

ANTI-AMYLOID THERAPIES HAVE BEEN FDA APPROVED FOR THE TREATMENT OF ALZHEIMER’S DISEASE

On July 6th, 2023, the FDA announced traditional approval for the anti-amyloid monoclonal antibody therapy, lecanemab, for treatment of Alzheimer’s disease.

One year later, on July 2, 2024, the FDA approved the second anti-amyloid monocloncal antibody therapy, donanemab, for treatment of Alzheimer’s disease.

FDA ANNOUNCEMENT

The Center for Medicare and Medicaid Services (CMS) also announced that monoclonal antibodies that target amyloid (or plaque) for the treatment of Alzheimer’s disease that receive traditional approval from the FDA under coverage with evidence development (CED). CMS, as a part of this decision, will provide enhanced access and coverage for people with Medicare participating in CMS-approved studies, such as a data collection through routine clinical practice or registries. In other words, patient will need to be in a study that collects clinical information into a clinical database. They will not need to be enrolled in a clinical trial.

CMS STATEMENT

As part of the coverage with evidence development (CED), CMS requires that all Medicare patients must be enrolled in a CMS approved clinical registry. The CNU at the BIDMC is the first center (and only 1 of 2) that has a CMS approved clinical registry. We are currently enrolling patients seen in our DiAD clinic into our CMS approved registry and treating Alzheimer’s patients with anti-amyloid therapies, including lecanemab.

LIST OF CMS APPROVED REGISTRIES

These medications are only available to patient with CSF or amyloid-PET confirmation of amyloid. The medications require intravenous infusions (done through the BIDMC infusion clinic) and there is a small risk for brain swelling and brain bleeding while on the medication. Medicare will cover 80% of the $26,500 annual cost of this medication.

Patients: If you are interested in learning more about anti-amyloid monoclonal antibody therapy, please call the Cognitve Neurology Unit to schedule an evaluation in our DIAD clinic.

Healthcare providers: If you have patients who are interested in learning more about lecanemab and donanemab, you can refer them to the Cognitive Neurology Unit.

Please provide your name and the patient’s name, date of birth, and email address. If the patient has completed a recent Montreal Cognitive Assessment (MoCA), Mini Mental Status Exam (MMSE), MiniCog, or AD8 Dementia Screening Interview please include those scores as well. Providing a disease severity stage through the very quick Functional Assessment Staging (FAST) would be helpful.

FAST STAGE:

1. No difficulties, either subjectively or objectively.
2. Complains of forgetting location of objects. Subjective word finding difficulties.
3. Decreased job function evident to co-workers;
   difficulty in traveling to new locations. Decreased organizational capacity.*
4. Decreased ability to perform complex tasks (e.g., planning dinner for guests), handling personal finances (forgetting to pay bills), difficulty marketing, etc.
5. Requires assistance in choosing proper clothing to wear for day, season, occasion.

LECANEMAB

CLICK HERE FOR MORE INFORMATION ABOUT LECANEMAB

The FDA has approved lecanemab for the treatment of Alzheimer’s disease.

Intravenous (IV) lecanemab

Lecanemab is a monoclonal antibody developed by Biogen in partnership with Eisai that removes beta-amyloid from the brain. It is administered by intravenous infusion over approximately one hour every two weeks for 18 months. This amounts to approximately 26 infusions in one year and 40 infusions over 18 months. The infusions occur at a BI-Lahey infusion center or an approved private infusion clinic in collaboration with our institution. Patients also require at least four brain MRI scans at BIDMC and six clinic visits during the first year of treatment.

FDA ANNOUNCEMENT

Subcutaneous (SQ) lecanemab

On July 13, 2026, the FDA approved subcutaneous lecanemab (lecanemab-irmb) as a starting regimen for adults with early Alzheimer’s disease. During the first 18 months, the approved dose is 500 mg once weekly, administered as two 250 mg autoinjector injections. After appropriate training, the injections may be administered at home by the patient or a caregiver. The selected SQ dose produces drug exposure comparable to the approved IV regimen. However, SQ lecanemab has not been evaluated separately in a large randomized, placebo-controlled clinical efficacy trial. Its expected efficacy is based on the demonstrated efficacy of IV lecanemab, together with comparable drug exposure and amyloid-plaque reduction. At BIDMC, the eligibility testing protocol, clinical follow-up schedule, and MRI monitoring schedule will be the same for IV and SQ lecanemab. We are working with the BILH Pharmacy to make SQ lecanemab available and anticipate offering it in late autumn 2026.

FDA ANNOUNCEMENT ON SUBCUTANEOUS LECANEMAB

DONANEMAB

CLICK HERE FOR MORE INFORMATION ABOUT DONANEMAB

The FDA has approved donanemab for the treatment of Alzheimer’s disease.

Donanemab is a monoclonal antibody developed by Eli Lilly that removes beta-amyloid from the brain. It is administered by intravenous infusion over approximately 30 minutes every four weeks. The infusions occur at a BI-Lahey infusion center. Patients require MRI monitoring and clinical follow-up during treatment. The overall benefit-risk profiles of donanemab and lecanemab appear broadly similar, with similar magnitudes of clinical benefit in their respective pivotal trials, although the two medications have not been compared directly in a randomized trial. We use the FDA-approved gradual-titration regimen, increasing the dose during the first four monthly infusions—350 mg, 700 mg, 1,050 mg, and then 1,400 mg from the fourth infusion onward. In our experience with this regimen, infusion-related reactions and MRI-detected complications have been similar to those observed with lecanemab.

LECANEMAB MAINTENANCE THERAPY AT BIDMC

The FDA label permits lecanemab maintenance dosing after 18 months, either by intravenous infusion every four weeks or by weekly subcutaneous injection. BIDMC reviewed the available evidence and concluded that no randomized controlled study has demonstrated the clinical efficacy of these maintenance regimens. The maintenance regimens are supported primarily by pharmacokinetic and pharmacodynamic modeling and open-label biomarker data, without any clinical evidence of benefit. After 18 months of standard therapy, amyloid has been substantially reduced in most patients, and approximately two-thirds have amyloid levels below the threshold for amyloid positivity. In BIDMC’s assessment, this further reduces the rationale for continued anti-amyloid therapy. Therefore, BIDMC is not currently offering lecanemab maintenance therapy.

ADUCANEMAB   

In June 2021, the FDA approved aducanumab to treat patients with Alzheimer’s disease using the Accelerated Approval pathway, under which the FDA approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug’s clinical benefit.

The CNU and the BI-Lahey Pharmacy and Therapeutics Committee reviewed the aducanumab data and determined that there is insufficient evidence of benefit to warrant offering this medication to our patients. The Centers for Medicare and Medicaid Services have recommended Biogen run an additional clinical trial to verify the clinical benefit of aducanumab. The CNU will be one of the centers involved in this clinical trial.

If you are interested in participating in this or other clinical trials at the BIDMC, please contact: Memory Research Coordinator 617-667-0249 / alz@bidmc.harvard.edu.