The European Medicines Agency (EMA) has announced the release of a new concept paper calling for the revision of its guideline on the development of products intended to treat Alzheimer's disease "and other dementias," saying a new approach is needed to accommodate patients who are pre-symptomatic or in the early stages of disease progression.

The Need for a Guideline

The concept paper is similar to a draft guidance released in February 2013 by the US Food and Drug Administration (FDA), which also noted the need to support treatments intended to prevent the onset of overt dementia.

"The underlying anatomical and pathophysiologic changes in AD begin many years before clinical symptoms emerge," FDA explained. "We recognize that the standard approaches to the selection of outcome measures historically used in the development of treatments for dementia of the Alzheimer's type have major limitations when applied to clinical trials enrolling patients in the early clinical stages of the disease, or before clinical impairment has emerged at all."

EMA seems to agree with that assessment, at least in theory. "[P]opulations of early and even pre-symptomatic patients are being included in clinical development programs," it wrote. "The inclusion of prodromal patients might enable treating individuals, hypothetically, at a time when some drugs may be more effective than they would be later in the illness. These changes need consideration in a revision of the current AD guidance as e.g. assessment tools need to be more sensitive and the requirement of two co-primary endpoints addressing improvement of cognition and functional activities of daily living is not feasible in in such a patient population."

Major Problems

Similar to FDA, EMA said the biggest challenge of all seems to be the correct utilization of diagnostic criteria, particularly at early stages of the disease when it can be difficult to measure outcomes. EMA said it hopes that new research diagnostic criteria, biomarkers and outcome measures can be used by companies to satisfy regulators' safety and efficacy concerns.

Regulators also said any future guideline should take into account the use of different parameters and assessment tools in different stages of the disease, different assessments of safety and efficacy in different age groups, the design of long-term safety studies, and the usefulness of combination therapy and how those therapies should be studied.

An updated guidance should be available within six months of the adoption of the concept paper, EMA wrote. Comments on the draft are due by 31 January 2014.

EMA Draft Concept Paper

EMA Press Statement