The mental, physical, and economic impact of the disease is expected to increase exponentially in the coming years.  Today, more than 30 million people have AD, and the associated cost of care exceeds $200 billion annually.   The 2009 World Alzheimer’s Report stated the number of people with dementia would reach 135 million by 2050² .  The 2013 G8 Dementia Summit issued a policy brief³, which estimates there will be a 17% increase in the number of people living with dementia.

There is no cure for AD.  Although symptomatic drugs (e.g., acetylcholinesterase inhibitors and the NMDA-antagonist memantine) are available, they only produce limited cognitive and functional benefits that are not sustained over time.  In 2012, we learned a great deal from two Phase 3 clinical programs, which were testing two separate compounds targeting amyloid beta (Aβ) clearance in mild to moderate AD patients.  First, the results highlighted the growing recognition that it is very difficult to affect changes in the brains of patients with established symptoms of the disease.  Second, attempting to treat when symptoms have appeared is likely too late to have a positive impact on delaying or stopping disease progression; the damage is already done⁴.  In early 2013, the U.S. Food and Drug Administration (FDA) issued important new draft guidelines intended to facilitate drug development targeting early stages of Alzheimer’s disease⁵.

There are large gaps in our understanding of AD, yet significant advances have been made, particularly in the past five years, that are cause for optimism.  Our understanding of AD has increased significantly as the result of new insights from research in preclinical models, genetic screening of large patient populations to identify new risk factors, and clinical trial experiences, including biomarker studies conducted at different stages of the disease, as well as in genetically defined patient populations.  On one hand, these findings strengthen our belief regarding Aβ accumulation is the initiator of the neurodegenerative cascade, beginning ten to 20 years before symptoms appear.  On the other, they highlight the importance of ensuing synergistic biochemical changes that occur very early in the disease process, such as inflammation, oxidative stress, and tau pathology, which result in irreversible damage.

While the majority of clinical trials have tested patients with mild to moderate AD, the emphasis now has shifted almost entirely towards disease modification at the earliest stages of the disease, even before symptoms occur by selecting individuals based on biomarkers or genetic risk factors.  Identifying patients who have Mild Cognitive Impairment (MCI) who are most likely to advance to AD requires multiple biomarker and imaging technologies is critical to the success of clinical trials because the disease has significant variability amongst patients: the age of disease onset, the rate of decline in cognition in the predementia phase, and the relatively low annual rate of progression to disease stage in the general population.  By employing a patient-enrichment strategy, the study’s sponsor increases the power of drug clinical trials and reduces both the required number of participants and the length of the study.

CereSpir is conducting extensive analysis into the most accurate and promising technologies to assist with patient selection for its Phase 3 clinical studies.  This analysis should allow the Company to reduce the inherent risk associated with late-stage development of any investigational compound and increase its opportunity to succeed.

Footnotes:

1. Alzheimer’s Association, 2013 Alzheimer’s Disease Facts and Figures, Alzheimer’s & Dementia, Volume 9, Issue 2
2. http://www.alz.co.uk/research/files/WorldAlzheimerReport.pdf
3. http://www.alz.co.uk/research/G8-policy-brief
4. Karran et al., .2011 Nature Rev Vol. 10: 698-712; McGeer & McGeer 2013 Acta Neuropathol 126:479–497
5. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM338287.pdf
6. Risacher et al., 2013 Frontiers in Aging Neurosci Vol. 5: 1-12