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As part of the Accelerated Approval pathway, the sponsor is required to conduct a post-market clinical trial to ensure endpoints are met. The sponsor has up to nine years to complete the trial. If the trial fails to show clinical benefit, the FDA could withdraw approval of the drug. The Â鶹´«Ã½Ó³»­ detailed alternative drug approval pathways in a policy brief.

Amyloid-related imaging abnormalities (ARIA) is the most common side effect in the clinical trials. ARIA was more common in patients with ApoE4 genotype. There are two types of ARIA, ARIA-E refers to vasogenic edema identified on FLAIR MRI sequences and ARIA-H microhemorrhages and hemosiderosis. ARIA is monitored through MRIs performed before an infusion unless a patient develops any symptoms in between infusions. While most cases of ARIA in the clinical trials were asymptomatic, a subset developed associated symptoms. Infusion reactions are also a possible side effect of this class of drugs.

The clinical trials included participants with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease. 

Patients with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease generally have a mini-mental state examination (MMSE) score between 24 and 30 out of 30 and a clinical dementia rating (CDR) of .5. Patients should have evidence of beta amyloid pathology before they receive any medication in this class. At this time, beta amyloid pathology can be determined through CSF analysis or completion of an amyloid PET scan. CMS will only authorize completion of one amyloid PET scan through coverage with evidence development. Specific criteria for treatment eligibility for each medication will be determined after FDA approval.

Clinical trials completed by manufacturers did not enroll individuals with Down Syndrome, although there was a strong movement with aducanumab for this patient population to have access to the drug. The NCD did not finalize exclusion criteria for patients with Down Syndrome and other intellectual and developmental disabilities. Patients with these conditions can be included in the RCTs.

CMS currently covers monoclonal antibody therapies under a coverage with evidence development (CED). A coverage with evidence development requires the use of a treatment in conjunction with an approved clinical trial.

Many private payers have determined they will follow current CMS guidance in regard to coverage for monoclonal antibody therapies. Some payers are following CMS guidance and only cover the treatment as long as it is part of an approved clinical trial. It is always encouraged to double-check the patient’s policy to see if they have coverage for this class of therapy. The Â鶹´«Ã½Ó³»­ continues to work with private payers on coverage as new therapies become available.

The Â鶹´«Ã½Ó³»­ may develop an Evidence in Focus article regarding the class of monoclonal antibody therapies for Alzheimer’s disease following FDA approval of these therapies.

The Â鶹´«Ã½Ó³»­ is working on developing education sessions, tools, and resources for members to aid in diagnosing, prescribing, treating side effects, and patient messaging.

While both products target amyloid beta plaque, the most significant difference is highlighted in the in late 2022, finding that  lecanemab was able to moderately slow decline on measures of cognition and function in patients with early AD and MCI relative to placebo at 18 months of treatment. The FDA announced traditional approval for lecanemab on July 6, 2023. Aducanumab is not being considered for traditional approval. 

Amyloid-related imaging abnormalities (ARIA) are the most common side effect in clinical trials. ARIA was more common in patients with ApoE4 genotype. There are two types of ARIA, ARIA-E refers to vasogenic edema identified on FLAIR MRI sequences, and ARIA-H microhemorrhages and hemosiderosis. ARIA is monitored through MRIs performed before an infusion unless a patient develops any symptoms in between infusions. While most cases of ARIA in the clinical trials were asymptomatic, a subset developed associated symptoms. Infusion reactions are also a possible side effect of this class of drugs. (This was taken from the monoclonal antibody Q&A.) The Â鶹´«Ã½Ó³»­ is developing an edition of "Emerging issues in neurology" to help our members understand the role lecanemab may play in the AD treatment landscape.

The FDA approved lecanemab for patients in the mild cognitive impairment or mild dementia stages of Alzheimer's Disease with proven amyloid beta pathology. 

Yes, lecanemab is covered by Medicare as long as the provider participates in a prospective comparative study. on this requirement. Lecanemab, and all other monoclonal antibodies for the treatment of Alzheimer's Disease (AD), are subject to this  (NCD) that was finalized by CMS in April of 2022 in response to the approval of aducanumab and the surrounding controversy.  

Yes, according to the , "lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events." The Â鶹´«Ã½Ó³»­ cited this finding in its letter to CMS requesting that the NCD that currently restricts access to lecanemab be reconsidered, as this has demonstrated direct clinical benefit. 

The Â鶹´«Ã½Ó³»­ submitted comments to CMS requesting that the NCD restricting coverage of lecanemab to randomized controlled trials be reconsidered. The Â鶹´«Ã½Ó³»­ has met with CMS on numerous occasions to discuss this issue and is working closely with the agency's Coverage and Analysis Group to determine the best path forward to ensure appropriate access to this therapy upon full approval of lecanemab.  

Amyloid-related imaging abnormalities (ARIA) are the most common side effect in clinical trials. ARIA was more common in patients with ApoE4 genotype. There are two types of ARIA, ARIA-E refers to vasogenic edema identified on FLAIR MRI sequences, and ARIA-H microhemorrhages and hemosiderosis. ARIA is monitored through MRIs performed before an infusion unless a patient develops any symptoms in between infusions. While most cases of ARIA in the clinical trials were asymptomatic, a subset developed associated symptoms. Infusion reactions are also a possible side effect of this class of drugs. (This was taken from the monoclonal antibody Q&A). The Â鶹´«Ã½Ó³»­ is developing an edition of "Emerging Issues in Neurology" to help our members understand the role donanemab may play in the AD treatment landscape.

Patients in the study were diagnosed with mild cognitive impairment or mild dementia stages of Alzheimer's Disease with proven amyloid beta pathology.

The Â鶹´«Ã½Ó³»­ submitted comments to CMS requesting that the NCD restricting coverage of donanemab to randomized controlled trials be reconsidered. The Â鶹´«Ã½Ó³»­ has met with CMS on numerous occasions to discuss this issue and is working closely with the agency's Coverage and Analysis Group to determine the best path forward to ensure appropriate access to this therapy upon full approval of donanemab. CMS has stated that the agency will continue to assess the developing body of evidence throughout the coverage with evidence development process prior to modifying requirements mandating participation in a prospective comparative study as a condition of coverage.