Adhulem and Lecanemab by Biogen Exciting Clinical Trials in the Alzheimer’s Space

Adhulem and Lecanemab in Alzheimer’s clinical trials.
 
Author: Rebecca Schlossberg

Alzheimer’s Disease (AD) is an age-related neurodegenerative disease which causes the brain to atrophy and brain cells to die resulting in loss of memory and cognitive functions. AD is the sixth leading cause of death in the US and affects approximately 24 million people worldwide. There are two types of AD, early onset (age 30-60) and Alzheimer’s dementia (age 65+). The exact cause of AD is still not fully understood but there seems to be a strong consensus about it occurring from a combination of genetic, lifestyle, and environmental factors. The disease mechanism, on a cellular level, results from a buildup of proteins that fail to function normally and disrupt neural networks, triggering a series of toxic events. The two proteins that have been the focus of AD research are Beta-amyloid and Tau proteins. Beta- amyloid is a fragment of a larger protein which when clustered together form amyloid plaques that disrupt cell-to-cell communication. Tau proteins play an integral part in a neurons internal support and transport system, carrying nutrients and other essential materials through the neural network. In AD, Tau proteins undergo a shape change and organize into neurofibrillary tangles which disrupt the transport system. This phenomenon results in toxic materials building up and prohibits nutrients from reaching neurons. Both protein dysfunctions are characteristic to AD and are clear contributors to the associated symptoms.

Currently there is no treatment that cures AD in its entirety. However, there are some medications and interventions that temporarily improve or slow the progression of the symptoms. There are some non-drug approaches being used such as physical activity regiments, specific diets, and cognitive training. A combination of these treatments is currently the preferred method for physicians right now, known as precision medicine. Included in this is also a slew of medications that have been FDA approved such as, Donepezil, Rivastigmine, Memantine and Galantamine. These treatments help to maximize function, maintain independence and to improve the quality of life for patients and their family members. However, none of the medications or treatments change the underlying disease process and as such are only effective for a limited time.

The first therapy to treat the disease process was recently developed and FDA approved in 2021 by Biogen. This drug, aducanumab, (brand name Aduhelm) was granted accelerated approval because of its exciting results in effectively removing beta-amyloid plaques, the hallmark of AD. This is the first drug to come out of the pipeline treating AD, in 18 years (McAlpine, 2021). Despite the approval there have been some barriers to successful distribution and promotion. The first being the cost of the drug; Aduhelm was priced at ~$56,000 per infusion. It was eventually slashed to $28,200 for a patient of average weight, However, this is still an astronomical price which most patients cannot afford. Additionally, most insurance companies are not sure how much, if any, they want to cover. Recently Medicare, the insurance that covers most Alzheimer’s patients in the US, announced that they would cover the treatment cost, however, economists have said this would most likely cause the US government to go into enormous debt in just a few years (Press, 2021)​.

Biogen has also come under fire for adhulem’s wide-labeled approval. Following this fiery criticism the company made a surprising move in July of 2021 to narrow the label and only recommend the drug for those with milder AD cases.  

Another barrier to entering the market is that many physicians are noticing that Biogen has yet to establish a true link between the results of their studies and patient benefit. Due to these concerns, some government regulatory agencies have opened investigations into the benefits and efficacy of the drug. Additionally, the FDA commissioner herself, Janet Woodcock, M.D., has requested that the inspector general conduct an independent inspection into the regulations decision to approve Biogen’s Adhulem. 

Biogen has also been under scrutiny from the FTC and SEC, each launching their own investigation into Aduhlem. In February 2022, the FTC made a civil investigative demand to receive documents related to Aduhlem’s marketing and approval. The SEC also is interested in investigating marketing and approval. 

Due to all of these challenges in rolling out the drug, Aduhelm has performed very poorly in sales. The drug made just one million for the fourth quarter and $3 million for all of 2021. This pales in comparison to the hundreds of millions of dollars put into the developing, manufacturing, and selling the drug. 

Interestingly, there is a new drug in the works to treat AD, also being developed by Biogen and their Japanese partner Eisai, Ban2401 (brand name lecanemab). This drug also targets beta-amyloid proteins and is currently under investigation in two clinical trials for patients with early-stage AD. The clinical trials are being conducted to confirm safety and efficacy of Lecanemab in participants with Early Alzheimer’s Disease. The first study is a Phase 2 clinical trial investigating the tolerability and determining the dosing of Ban2401 on 856 patients. This study is set to be completed in March of 2022.  A second study is also simultaneously being conducted with a larger population size to confirm results of the first study. This is a phase 3 randomized double-blind clinical trial looking at 1766 participants over the course of 18 months. Given that this drug is still in clinical trials there is much that is still unknown about how it will be received and whether it will be successful.

The fact that Biogen is so determined to create a drug to treat AD, indicates that there is a very big market and large profit potential. 1 in 9 people 65 years and older suffer from AD. The number of people with AD in the US alone is 8.5 million and is sure to grow year after year with population growth. Additionally, the average lifespan is also increasing which will add to the incidence of the disease. Other factors that will contribute to further market growth are advances in diagnostic tools and increased social awareness. According to a consulting firm, GlobalData, the market for AD treatment will more than double in the next 10 years with a CAGR of 10.5%. Aduhelm and lecanemab both have large market potentials, but the question will remain on whether they will truly be effective in treating the underlying processes of Alzheimer’s Disease.

 

Press, T. A. (2021, June 10). Medicare Copays For New Alzheimer’s Drug Could Reach $11,500 Annually. NPR. https://www.npr.org/2021/06/10/1005319693/medicare-copays-for-new-alzheimers-drug-could-reach-11-500-annually

McAlpine, K. (2021, June 7). FDA Approves First Alzheimer’s Treatment in 18 Years. Now What? Boston University. https://www.bu.edu/articles/2021/fda-approves-first-alzheimers-treatment-in-18-years-now-what/

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