Comments invited on concept paper on the need to revise the guideline on medicines to treat Alzheimer's disease

31 October 2013

The European Medicines Agency has released a Draft concept paper on need for revision of the guideline on medicinal products for the treatment of Alzheimer's disease and other dementias - Revision 1 for public consultation.

Comments should be sent by 31 January 2014 to [e-mail], using the template provided.

Recent progress in understanding the neurobiology and pathophysiology of Alzheimer's disease suggests that the structural and biological changes associated with the disease start to occur as early as 10 to 20 years prior to the emergence of the clinical symptoms. As a consequence, early and even pre-symptomatic patients are now being included in clinical development programmes and it is expected that some medicines may be more effective at that stage than they would be later in the illness.

New research diagnostic criteria are being used in clinical trials for different stages of the disease. In addition, a number of biomarkers to help identify and select patients at the pre-dementia stage of the disease have been developed by medicines developers; several have received a qualification opinion from the Agency's Committee for Medicinal Products for Human Use (CHMP) for use in the development of medicines.

The concept paper describes how these new developments have had an impact on recent and future clinical-trial protocols and discusses the elements to consider as part of the revision of the current guideline. These include the:

• impact of new diagnostic criteria for Alzheimer's disease, including early and even asymptomatic disease stages on clinical-trial design;
• choice of parameters to measure trial outcomes and the need for distinct assessment tools for the different disease stages in Alzheimer's (different signs and symptoms, differences in change over time, severity);
• assessment of efficacy and safety in different age groups;
• potential use of biomarkers and their temporal relationship with the different phases of Alzheimer's disease at different stages of medicine development (mechanism of action, use as diagnostic test, enrichment of study populations, stratification of subgroups, safety and efficacy markers, etc.);
• design of long-term efficacy and safety studies;
• usefulness of combination therapy and corresponding study designs.

The comments submitted on the concept paper will be considered in the development of the revised guideline.