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Launched in 2009, the rationale for the RMS® Longevity Risk Model was to bring state-of-the-art developments in the science of aging to the life insurance industry. The traditional actuarial approach has been retrospective, based on a statistical analysis of past mortality. Understanding the medical drivers of mortality is crucial for data analysis.

The 1918 influenza pandemic caused a significant dip in mortality improvement, as has COVID-19. And as shown in the figure of U.S. deaths due to dementia in 2020, compared with previous years[1], COVID-19 has been especially difficult for those with dementia. 

Unable to comprehend coronavirus restrictions, the social isolation of many dementia sufferers has contributed to premature mortality. Furthermore, those with COVID-19 were at significantly increased risk of a new diagnosis of Alzheimer’s Disease (AD), which is the most common form of dementia[2].

U.S. deaths due to dementia in 2020, compared with the 2015-2019 average
Figure 1: U.S. deaths due to dementia in 2020, compared with the 2015-2019 average. Source: Alzheimer’s Association

At the triennial Society of Actuaries (SOA) 2023 Living to 100 Symposium, held in Orlando in mid-January, I presented on the importance of cognitive health for pandemic survival and longevity.

One of the concerns for the future is that Long COVID may give rise to an increased prevalence of dementia among the elderly[3]. Cognitive decline is the biggest factor in determining how long patients with AD will live after being diagnosed. So, effective medical treatment for reducing the cognitive decline of those with AD is urgently needed.  

Prior to the launch of the RMS Longevity Risk Model, I attended the SOA Living to 100 Symposium in 2008, which charted the extended longevity horizon in the 21st century.

Centenarians are noted for having less of a build-up in the brain of amyloid plaques, which are associated with AD. This has motivated the search for a drug to reduce brain amyloid levels and demonstrate a significant reduction in cognitive decline.

However, for several decades, this search has not been successful, despite the allocation of substantial pharmaceutical funding. With an estimated 6.5 million Americans living with AD in 2022, the upside revenue potential for AD drug development is very attractive for the pharmaceutical industry.

At last, some promising news was presented at the 15th Clinical Trials on Alzheimer’s Disease conference in San Francisco on November 29, 2022.  Pharmaceutical companies, Eisai and Biogen, headquartered in Tokyo and Cambridge, Mass., announced the full results of a Phase 3 trial of Lecanemab for reducing cognitive decline from AD.

At eighteen months, Lecanemab showed a significant reduction in brain amyloid levels associated with early onset AD and slowed the decline of cognitive function on a clinical outcomes scale by 27 percent. Lecanemab is the first potentially disease-altering therapy for AD to make it through Phase 3 trials. 

On January 6, 2023, the U.S. Food and Drug Administration approved Leqembi (the U.S. brand name for this drug) via the accelerated pathway for the treatment of Alzheimer’s disease.

As an antibody therapy, Lecanemab is given intravenously every two weeks and must be given in sufficient doses so as to cross the blood-brain barrier efficiently. Ensuring a sufficient dose to the brain may give rise to side effects. According to Eisai, no deaths in the clinical trials could be attributed to Lecanemab.

Modeling simulations by Eisai suggest that Lecanemab may slow the rate of disease progression by 2.5 to 3.1 years and has the potential to help people remain in the earlier stages of AD for a longer period of time. In addition, it was shown to maintain the health-related quality of life and reduce the burden on caregivers.

According to Eisai and Biogen, the convergence of evidence across cognition and function, disease progression, health-related quality of life, and caregiver burden demonstrate that Lecanemab treatment may provide meaningful benefits to patients, their care partners, physicians, and society.

In a news release, Christopher A. Viehbacher, President and CEO of Biogen said “The approval of Leqembi provides new hope to patients with Alzheimer’s disease. Patients at an early stage of the disease and their caregivers can now consider a new treatment option with their doctors. Our focus now is on the path forward, working alongside Eisai with the goal of making Leqembi available to patients who may benefit from this treatment as soon as possible.”

For many families, the availability of this AD treatment will be at the top of their wish list for the New Year.

 

[1] Alzheimer’s Association, 2021

[2] Wang L., Davis P.B. et al. J. Alzheimer’s Disease, 2022

[3] Lauria A., Carfi A. et al. Clinics in Geriatric Medicine, 2022

 

 

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Gordon Woo
Gordon Woo
Catastrophist, RMS

Gordon is a catastrophe-risk expert, with 30 years’ experience in catastrophe science, covering both natural and man-made hazards. Gordon is the chief architect of the RMS terrorism risk model, which he started work on a year after joining RMS in December 2000. For his thought leadership in terrorism risk modeling, he was named by Treasury & Risk magazine as one of the 100 most influential people in finance in 2004. He has since lectured on terrorism at the NATO Center of Excellence for the Defense against Terrorism, and testified before the U.S. Congress on terrorism-risk modeling.

As an acknowledged, international expert on catastrophes, Gordon is the author of two acclaimed books: “The Mathematics of Natural Catastrophes” (1999) and “Calculating Catastrophe” (2011). Dr. Woo graduated as the best mathematician of his year at Cambridge University and he completed his doctorate at MIT as a Kennedy Scholar and was a member of the Harvard Society of Fellows. He also has an Master of Science in computer science from Cambridge University.

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