FDA Approves First Treatment of Alzheimer’s Disease in Almost 20 Years

Vincent S. DeOrchis, MD MS - Director of Neurology - St. Francis Hospital and Heart Center, Roslyn NY

November 24, 2021

November marks arrival of National Alzheimer’s Disease Awareness Month. This year brings a particularly complex and often opinionated perspective on the course of disease treatment. On June 7, 2021, the FDA made a controversial and unexpected decision to greenlight a novel therapy for Alzheimer’s disease, the first approved for this condition since 2003. ADUHELM (aducanumab), manufactured by Biogen, marks a new class of cognitive therapy – a monoclonal antibody directed at amyloid beta aggregates and soluble oligomers, the pathologic hallmark of Alzheimer’s disease.

On the surface such news would suggest great celebration within the neurologic community but the devil lies in the details. The Phase III clinical trial upon which the application of this medication was based was halted initially in March 2019 after preliminary data suggested it would not meet its primary end point. In October of the same year Biogen announced that further analysis of a larger data set suggested that the drug was in fact effective based on the reduction of amyloid beta plaque burden as determined by PET imaging – however clinical improvement was not well demonstrated (0.6% change on a 30 point mini mental status exam (MMSE)).

One month later the FDA established a panel of outside experts in cognition and dementia who reviewed the details of the clinical trials and concluded that aducanumab “failed to show strong evidence” of its reported effectiveness and did not recommend it be approved. They also cited multiple “red flags” found within the data analysis.

Despite these expert recommendations as well as extensive support within the neurologic and scientific community backed by editorials written in multiple peer reviewed journals, the FDA provided a “conditional” approval for aducanumab on June 7, 2021.

This decision resulted in a flurry of frantic phone calls from patients demanding access to this treatment without knowledge of it’s $56,000 per year cost, which has thus far not been covered by the Center for Medicare Services (CMS), or the need to identify underlying amyloid-beta disease on a amyloid-PET scan (also not covered by Medicare) or undergo a lumbar puncture to assess CSF amyloid levels. Despite these Everest-size hurdles, there were further issues such as an approximately 25% incidence of cerebral edema, 21% incidence of headaches and 19% incidence of microhemorrhages requiring serial imaging to monitor.

Finally, and possibly most importantly, the clinical trials supporting this agent only investigated patients with “mild Alzheimer’s disease,” yet the FDA initially approved the drug for all stages. This was later reversed to include only mild stages of the illness. The Kaiser Family Foundation (KFF) suggested if 500,000 Medicare patients received aducanumab (6 million American’s are estimated to suffer from Alzheimer’s dementia), the estimated cost to Medicare would be $29 billion per year. To put this into perspective, total Medicare spending for all doctor-administered drugs in 2019 was $37 billion.

Neurological Associates of Long Island, PC has a number of skilled practitioners with extensive experience in diagnosing, treating and managing patients with neurodegenerative diseases. In particular, Doctors Vincent DeOrchis, David Podwall, Michael Han and Tracy DeAngelis who have acted as either Principal Investigators or Sub-Investigators on a number of clinical research trials evaluating the safety and efficacy of novel therapeutic agents in the treatment of Alzheimer’s type dementia including the EPOCH trial, the SteadFast trial, the Insomnia in Alzheimer’s Patients Study and the ongoing Graduate I trial.

The “conditional” nature of the FDA approval as part of the “accelerated approval process” for aducanumab implies the manufacturer, Biogen, will have to submit further data as part of a post-market study. The neurology providers at Neurological Associates of Long Island, PC are ready and waiting to participate in this trial and look forward to providing the necessary clinical data to determine whether this novel agent is simply cleaning the ash left behind by the fire, or if there is truly clinical benefit associated with reduction of amyloid beta burden. Regardless of the outcome, our investigators will continue to participate in the investigation of future drug candidates.

Alzheimer’s disease is a devastating illness with few effective treatments available and profound repercussions for patients and care-givers alike. An effective, safe, economical and universally available treatment is paramount. We remain an eager and excited participant in the search for a cure.