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Q: What does the Accelerated Approval pathway mean for monoclonal antibody directed against the treatment of Alzheimer’s disease therapies?    
A: 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 AAN detailed alternative drug approval pathways in a recent policy brief.

Q: What are the side effects associated with these therapies?   
A: 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.

Patient identification 

Q: What patient population can access these therapies? 
A: The clinical trials included participants with mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease. 

Q: How will treatment eligibility be determined?   
A: 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.

Q: Are patients with Down syndrome eligible for any of these therapies?    
A: 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

Coverage

Q: What will Center for Medicare & Medicaid Services (CMS) cover for diagnosis and treatment?  
A: 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.

Q: What will private payers cover for diagnosis and treatment?  
A: 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 AAN continues to work with private payers on coverage as new therapies become available.

ºÃÉ«ÏÈÉú and tools 

Q: Will the AAN be developing any guidelines for monoclonal antibodies?  
A: The AAN may develop an Evidence in Focus article regarding the class of monoclonal antibody therapies for Alzheimer’s disease following FDA approval of these therapies.

Q: Will there be any education for members surrounding prescribing and treatment of monoclonal antibody therapies?   
A: The AAN is working on developing education sessions, tools, and resources for members to aid in diagnosing, prescribing, treating side effects, and patient messaging.