More than 6 million Americans and 55 million persons worldwide are living with dementia. Alzheimer’s disease (AD) is the most common form of dementia and may contribute to 60–70% of cases. However, dementia describes only the end stage of Alzheimer’s disease (AD). New estimates indicate that 416 million persons worldwide are currently living with the AD disease across the disease continuum – a number driven by an estimated ~300 million individuals worldwide living with preclinical AD. As the U.S. population aged 65 and older continues to grow, so too will the number and proportion of Americans with AD or other dementias. Without meaningful and effective therapies, the number of people with confirmed Alzheimer’s disease dementia is projected to rise to nearly 13 million within the United Stated by 2050 and 153 million worldwide. This estimate does not include persons in the predementia stages of disease, which provides a window of opportunity for prevention.
While two disease-modifying therapies (aducanumab and lecanemab) have received regulatory (FDA) approval over the last few years, there is still a critical need for continued development of novel therapeutic interventions to address the complete spectrum of people living with AD, considering the vast heterogeneity in the underlying biology and pathological progression of the disease. Challenges in clinical research and drug development include selecting the optimal patient population for evaluating novel mechanisms of action (patient stratification), ability to pick up the earliest signals of the disease (early stages of AD including pre-symptomatic), selection of the right endpoints and outcome assessments, molecular signatures of disease biology and pathology (biomarkers), treatment effect assessments, and correlations of the outcome assessments with clinical meaningfulness.
CPAD is a global, neutral convener, bringing together diverse stakeholders across industry, regulatory agencies, and academia within a pre-competitive forum under a data-driven, regulatory framework to accelerate therapeutic innovation in AD.
Leveraging the intellectual brain power and wealth of scientific knowledge gained from patient-level data contributions within the CPAD consortium, we identify the most critical unmet needs in AD and use our core competencies in data management, aggregation, and analysis, to facilitate informed decision making in AD drug development.
Addressing critical unmet needs in Patient-Focused Drug Development (PFDD) by incorporating the voice of patients, drug developers in industry and academia, and regulatory agencies
Focus on Model-Informed Drug Development (MIDD) through generation of novel, regulatory-endorsed quantitative drug development tools (DDTs) and solutions
Therapeutic innovation, optimization of trial design, development of novel analytical and statistical methodologies aimed at meaningful therapies in Alzheimer’s disease
CPAD’s regulatory success include the development of:
- Two clinical trial simulation tools:
- for mild-to-moderate AD which received endorsements from EMA and FDA (2013); and
- for amnestic mild cognitive impairment which received a Letter of Support (LOS) from EMA (2018).
- Endorsement from EMA (2011) and a LOS from FDA (2015) for hippocampal volume as an enrichment biomarker in AD trials.
- A LOS from FDA for exploratory prognostic biomarkers in cerebral spinal fluid (CSF) analytes for enrichment in AD trials (2015).
CPAD is currently leading the following pre-competitive working groups :
- Tau-PET Harmonization Working Group: Aims to validate a scale to quantify tau deposition across cohorts and tracers, which will facilitate a comparable and generalizable evaluation of the underlying biology and pathophysiology of tau deposition in the complete spectrum of AD progression, from early to late stages.
- Tau-PET Surrogacy Working Group: Aims to evaluate the evidentiary considerations needed for utility and acceptance of tau deposition and changes in tau following treatment as a reasonably likely surrogate endpoint in AD.
- Quantitative Modeling Working Group: Conducts quantitative analyses to better understand the underlying biology of AD and to develop disease progression models that will serve as the basis for quantitative models and clinical trial simulation tools used to facilitate informed decision making in the drug development process and optimize patient and endpoint selection, as well as the design of efficacy studies.
For more details see https://c-path.org/programs/cpad/tools-and-teams/working-groups/
“The compelling value proposition for contributing clinical trial data to CPAD included the structure of CPAD as a neutral convener and the opportunity to supplement with high-quality clinical data from other contributors, for the goal of developing regulatory-grade quantitative tools to support drug development, regulatory approvals and access.”
– Michael C. Irizarry
SVP & Deputy Chief Clinical Officer, Eisai & CPAD Industry Co-Director