Breakthrough Clinical Results
Voyager Therapeutics announced a new wholly-owned Alzheimer's disease (AD) program targeting apolipoprotein E (APOE), a major genetic risk factor for AD. This program utilizes an IV-delivered TRACER™ capsid to deliver a bifunctional payload designed to reduce APOE4 (high-risk variant) while increasing APOE2 (protective variant). Preclinical data showed significant reductions of APOE4 and increases in APOE2 in APOE4 knock-in mice. This addition complements Voyager's existing AD portfolio, including the clinical-stage anti-tau antibody VY7523 and gene therapies targeting tau and amyloid. Early data from this new program is anticipated at a future scientific meeting in 2025. Voyager's AD franchise aims to address tau, amyloid, and APOE, believing a combination approach will improve patient outcomes.
Key Highlights
- New wholly-owned Alzheimer's disease program targeting APOE, a major genetic risk factor.
- Uses IV-delivered TRACER™ capsid with a bifunctional payload to modulate APOE expression.
- Preclinical data showed significant reduction of APOE4 and increase of APOE2 in mice.
- Expands Voyager's existing Alzheimer's disease franchise targeting tau and amyloid.
Incidence and Prevalence
Global Alzheimer's Disease Burden: Latest Estimates
Prevalence
According to recent data, the global prevalence of Alzheimer's disease (AD) and other dementias reached 52,560,253.51 cases (95% CI: 41,399,948.84 to 65,633,448.71) in 2021. Specifically for Alzheimer's disease alone, cases have increased dramatically from 4.078 million in 1992 to 9.837 million in 2021.
Alzheimer's disease has affected more than 40 million people worldwide, with projections indicating this figure will significantly increase in coming decades. In fact, projections suggest a near fourfold increase in AD cases by 2050, driven primarily by population growth and aging.
Incidence
In 2021, approximately 9.84 million new cases of AD and other dementias occurred globally. The global age-standardized incidence rate (ASIR) has remained relatively stable from 1992-2021, rising slightly from 117.7 to 119.8 per 100,000 population.
Future projections indicate that by 2036, global AD cases will reach 19.117 million, with an ASIR of 418.92 per 100,000.
Demographic Patterns
Women consistently exhibited higher incidence rates than men across all regions. Additionally, the burden of early-onset dementia (EOD), defined as dementia in individuals aged 40-64 years, has nearly doubled from 1990 to 2021, reaching 7.758 million cases.
Regional Variations
The ASIR increased significantly in high-middle and middle-sociodemographic index regions but declined in low-sociodemographic index regions. In 2021, EOD burden was highest in high-middle and middle SDI countries, particularly rising during the COVID-19 pandemic.
During the COVID-19 pandemic (2019-2021), prevalence and DALY rates in high-SDI countries declined, while other SDI regions saw an accelerated increase.
Mortality and Disease Burden
In 2021, global mortality from AD and other dementias among individuals aged 60 and older reached approximately 1,922,970.75 cases (95% CI: 480,348.08 to 5,104,315.95). The fastest increase in age-standardized death rate was in low-middle SDI quintiles, with estimated annual percentage changes of 0.41%.
AD and other dementias caused 36.33 million disability-adjusted life years (DALYs) in 2021, representing substantial global health burden.
Risk Factors
High Body Mass Index (BMI) and High Fasting Plasma Glucose (FPG) were identified as prominent risk factors for AD. For early-onset dementia, high fasting plasma glucose was the most significant attributable risk factor for EOD-related DALYs globally.
The burden attributable to high BMI was increasing, whereas the burden associated with smoking steadily decreased. The Population Attributable Fractions (PAFs) for high body mass index and high FPG increased in nearly all regions since 1990.
These findings highlight the growing global burden of Alzheimer's disease and dementias, with significant regional variations and changing risk factor profiles that require targeted public health interventions.
Economic Burden
Economic Burden of Alzheimer's Disease in the USA
Direct Healthcare Costs
The economic burden of Alzheimer's disease (AD) in the United States is substantial. According to a 2017 report, the total payments in 2016 for health care, long-term care and hospice services for people age ≥ 65 years with dementia were estimated to be $236 billion. More recent estimates indicate that direct medical costs associated with Alzheimer's disease in the United States have exceeded $360 billion USD.
A 2024 study found that in the last 9 years of life, Alzheimer's disease added about 11% to the average $17,000 per year Medicare cost for same-risk beneficiaries without dementia. Average per-person Medicare payments for services to beneficiaries age ≥ 65 years with Alzheimer's disease and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great.
Indirect Costs and Caregiver Burden
The total annual indirect cost of Alzheimer's disease in the United States was estimated at $832 billion in 2024, which includes $599 billion in unpaid caregiving costs and $233 billion in productivity losses. In 2015, more than 15 million family members and other unpaid caregivers provided an estimated 18.1 billion hours of care to people with Alzheimer's and other dementias, a contribution valued at more than $221 billion. A 2019 study noted that according to the Alzheimer's Association, the economic value contributed by unpaid caregivers is $234 billion dollars.
Cost Variation by Disease Severity
The indirect costs increase with disease severity: $36,934 for mild cognitive impairment due to AD, $65,565 for mild AD, $103,717 for moderate AD, and $145,250 for severe AD (2024 USD).
Long-Term Care Costs
A 1992 study estimated nursing home charges for a cohort of AD patients to be between $4.3 and $6.4 million ($35,000-$52,000 per patient), with a median nursing home length of stay of 2.75 years. The combination of high rates of nursing home entry and lengthy stays makes long-term care the largest determinant of the cost of care in Alzheimer's disease.
Financial Burden Distribution
Unlike other diseases, families and Medicaid, rather than Medicare, bear most of the substantial cost burden of Alzheimer's disease and dementia. The costs of Alzheimer's care may place a substantial financial burden on families, who often have to take money out of their retirement savings, cut back on buying food, and reduce their own trips to the doctor.
Future Projections
As the population ages, the projected number of individuals suffering from dementia will nearly triple over the next 30 years, which will significantly impact healthcare costs. Currently, around 5 million people in the United States have Alzheimer's disease, and this prevalence is expected to rise dramatically in the coming decades due to the aging population.
Drug used in other indications
APOE Gene Therapy Beyond Alzheimer's Disease
Based on the available information, there is insufficient data to comprehensively detail which other indications beyond Alzheimer's disease are being trialed for APOE gene therapy using the TRACER™ capsid with bifunctional payload. The context provided does not contain specific information about additional indications or intervention models for APOE gene therapy trials.
The TRACER™ technology (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) represents an advanced approach in gene therapy delivery systems, but the specific non-Alzheimer's applications currently in clinical trials are not detailed in the provided information.
Similarly, information regarding the intervention methodologies, dosing protocols, and administration models for these potential trials is not available in the context.
For a comprehensive understanding of the current state of APOE gene therapy applications beyond Alzheimer's disease, additional research from clinical trial registries, scientific publications, or direct information from companies developing this technology would be necessary.
The therapeutic potential of APOE gene therapy likely extends to other neurological disorders and possibly metabolic conditions given the important role of Apolipoprotein E in lipid metabolism and neuronal function, but specific trials and their intervention models cannot be detailed from the available information.