Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Evaluation of Recent Scientific and Regulatory Developments in Alzheimer's Disease and Their Impact on the Clinical Development of a Disease-Modifying Therapy ***

Dr. Ulrich Heiser (Abschlußjahr: 2017)

Summary
Language: English
Alzheimer’s disease (AD) is the most common cause of dementia, with 10% of people aged 65 and older being affected. With its prevalence, also its huge economic impact becomes eminent. A new treatment approved by 2025, that delays the onset of AD by five years would reduce the number of people with the disease by 40% and also reduce the cost for care of AD-patients dramatically.
With research identifying early, possibly predictive biological markers for AD, diagnostic concepts where developed now considering a long symptom-free period before the clinical diagnosis. Regulators have accordingly adapted the guidance for AD drug development, based on the change of scientific paradigms.
Nevertheless, the causal mechanisms and progression factors for neuronal cell death and their link to the clinical appearance are still unknown. Supported by the identification of disease markers, a deeper insight into the pathogenic mechanisms became possible. However, up to now, a successful impact on the biological markers did not reliably translate into a positive clinical outcome and led to the failure of large pivotal clinical trials.
A close collaboration of medical/biological science, drug development and regulatory science should help to focus more on the pathology processes in view of the clinical effect in order to close the "neuropathological-clinical efficacy gap". With the regulatory support to validate surrogate efficacy markers, later also adaptive licensing processes might be considered in order to shorten the time for the drug until being available for the patients.
The clinical development of potentially disease-modifying drugs requests large trials with long treatment periods. With the expected effect size of disease modifying treatments being lower as for symptomatic approaches, the conduct of long clinical trials with a sufficient sample size have been and will remain necessary. This matter of fact entails the need for an improvement of means for patient recruiting and cohorting as well as the design of clinical trials in order to save time and resources and to ensure more reliable outcomes.
This thesis aims to collect an overview on the current understanding of AD and analyzes the status and current needs for the drug development of a disease modifying therapy in AD. This is done with regard to the scientific means, clinical trial conduct as well the role of regulators. The clinical development of the Glutaminyl Cyclase inhibitor PQ912 as a new potentially disease modifying AD therapy is put into this context.
Pages: 71
Annexes: 1, Pages: 2