Phase 3 Trials of Solanezumab and Bapineuzumab for Alzheimer's Disease

Salloway et al. (Jan. 23 issue)1 report on two trials of bapineuzumab in mild-to-moderate Alzheimer's disease, and in the same issue, Doody et al.2 report on two trials of solanezumab for this condition. The negative results of these phase 3 trials may be interpreted in two ways: either treatment was too late in the course of the disease or amyloid-beta (Aβ) alone is the wrong target for an effective treatment of Alzheimer's disease. The first interpretation may be clarified when the results of ongoing treatment trials involving persons with preclinical Alzheimer's disease are available. These trials include the Dominantly Inherited Alzheimer Network Trial (DIAN-TU; ClinicalTrials.gov number, NCT01760005), Alzheimer's Prevention Initiative (API; NCT01998841), and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease study (A4 Study; NCT02008357). The second interpretation has not yet been tested. Several tau-related vaccines are in advanced preclinical stages and will soon enter clinical trials. Since the pathologic process of Alzheimer's disease is characterized by the accumulation of both amyloid plaques and neurofibrillary tangles,3 it is reasonable to assume that a treatment strategy focusing on both targets may be more beneficial than a strategy focusing only on one.

NEJM 2014