Alzheimer’s Disease Snapshot - Prescient Healthcare Group

Alzheimer’s Disease: Current Trends and Future Outlook

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of cognitive function (specifically memory loss) and inability to conduct day-to-day tasks, which worsen as the disease progresses. It more commonly affects women and individuals aged ≥65 years.

April 2021

Sugandh Sharma, Senior Director and Manisha Chugh, Therapy Area Group Manager

Globally, 30-35 million individuals suffer from AD¹

Worldwide, 60-70% of 50 million people with dementia have AD, with greater prevalence in Western countries¹
This prevalence is predicted to double every 20 years until 2040²
About 10% of Americans aged ≥65 years have AD; in 2020, about 5.8 million Americans were affected¹
About 71% of the projected increase in the global prevalence of dementia by 2050 is likely to occur in low- and middle-income countries³

Sixth leading cause of death¹

Worldwide, 60-70% of 50 million people with dementia have AD, with greater prevalence in Western countries¹
This prevalence is predicted to double every 20 years until 2040²
About 10% of Americans aged ≥65 years have AD; in 2020, about 5.8 million Americans were affected¹
About 68% of the projected increase in the global prevalence of dementia by 2050 is likely to occur in low- and middle-income countries³

Global Alzheimer’s Therapeutic Market

The compound annual growth rate (CAGR) of 9.2% is attributed to an increase in the drug development pipeline for AD⁶
In 2019:
⁃ About 38.85% of the market was occupied by cholinesterase inhibitors
⁃ Pipeline drugs accounted for 31.15% of the market share
⁃ North America had the highest market share (29.3%)
The APAC was forecasted to grow at a CAGR of 6.2% during the same period

In 2020, $305 million was spend on AD care in the US⁴

The global cost of AD management is estimated to reach $2 trillion by 2030⁵
These costs include only measured disease management costs and do not consider other parameters, such as caregiver cost, cost implications of productivity loss and unemployment
In 2019, 16.3 million informal caregivers provided an estimated 18.6 billion hours of unpaid care in the US alone, which amounts to $244 million (assuming $13.11/hour)

No new therapy in the last 18 years

Even with a high prevalence and societal burden, there is a huge unmet need for AD patients. The greatest challenge is the lack of effective therapies to delay disease progression. AD has seen the highest rate of failure in trials (99.6%), with the last drug approval noted in 2003^7,8
Another major unmet need is appropriate tools for the early diagnosis of AD; about 29-76% of patients with dementia in primary care go undiagnosed⁸

AD Pipeline: A Highly Crowded Space With Increased Investment Despite Failures to Date

There are several ongoing studies in the AD domain. As at March 2021, there were 78 pharmaceutical products (biologics, small molecules, chemical entities and cell therapies) in Phase II and III trials. Among the molecules in Phase III trials, 76% are disease-modifying entities (such as anti-amyloid, anti-tau and anti-inflammatory); the rest are being developed to provide symptomatic relief from the agitation observed in 70-90% of patients with AD.

There are certain interesting novel classes among the pipeline products, including:

Vaccines

Vaccines against amyloid and tau proteins have the potential to prevent or halt the progression of AD
Data from the trials indicate that vaccines can generate antibody responses in the elderly population with very high antigen-specific titers

Stem Cells

Due to their regenerative potential, stem cells offer a unique approach for treating AD
Replacing the damaged cells with healthy cells can halt the progression of the disease rather than just slowing it or managing the symptoms

Gene Therapy

Gene therapy is a promising new frontier in AD treatment
Preclinical data have demonstrated reduced amyloid beta accumulation and neuroinflammation, as well as the recovery of normal brain functions

Catalyst Event Calendar for Phase III Assets During 2021-2022

Multiple catalyst events are expected to occur during 2021-2022. Key events for the Phase III assets are shown below:

Conclusion

The most anticipated drug for AD is Biogen’s aducanumab, an anti-amyloid beta antibody, which is currently awaiting an FDA decision (due June 7, 2021). If approved, it will be the first disease-modifying agent to be approved for AD and the first new therapy in 18 years; however, there are mixed opinions from experts on the likelihood of approval.

Other notable agents in advanced development stages are Roche’s gantenerumab and Lilly’s donanemab, both of which are designed to clear deposits of Aβ peptide plaques in the brains of AD patients.

For years, AD’s high disease burden has left patients and caregivers looking for novel therapies. Whether 2021 transforms the landscape of AD therapeutics remains to be seen; Prescient will monitor this closely.