Phase 3 results for the Alzheimer’s treatment solanezumab to be presented at the Alzheimer’s Association International Conference 2015
New data from an extended analysis of solanezumab — an anti-amyloid therapy tested in people with mild Alzheimer’s disease — will be presented at the Alzheimer’s Association International Conference (AAIC) 2015. The phase 3 extension follows 1,322 participants with mild symptoms and reports a sustained slowing of cognitive decline in those treated with the antibody, raising the possibility that solanezumab may have a disease-modifying effect.
Solanezumab completed two large phase III trials in 2012, known as Expedition and Expedition 2. Those trials did not meet their pre-specified primary endpoints in a combined population of patients with mild to moderate Alzheimer’s disease. However, a more detailed analysis of the trial data identified a clearer signal of benefit in the subgroup of patients with mild Alzheimer’s. Measures of memory, thinking and daily function showed modest improvements in that subgroup, prompting further investigation focused specifically on people in the early stages of the disease.
As a result, the research program moved forward with an additional phase III study (Expedition 3) targeted exclusively at individuals with mild Alzheimer’s. In parallel, investigators conducted an open-label extension of the original Expedition and Expedition 2 studies to better understand the longer-term effects of solanezumab when treatment is continued.
In the extension phase all participants who had been classified with mild Alzheimer’s were offered solanezumab, including those who had previously been randomized to placebo. The extension tracked treatment response over an additional two years, with some participants followed for up to three and a half years in total. Analyses from this longer follow-up indicate that participants who began solanezumab during the original phase III trials and remained on therapy throughout the extension experienced a slower rate of cognitive decline compared with those who received placebo initially and were switched to active treatment at the start of the extension.
In practical terms, the group treated continuously with solanezumab showed approximately a one-third reduction in the progression of problems with thinking and memory compared with the delayed-start group. Importantly, this relative benefit appeared sustained over the course of the three-and-a-half-year observation period, a pattern that is consistent with the possibility that solanezumab may be altering the underlying disease process rather than delivering only a short-term symptomatic effect.
Eric Karran, PhD, Director of Research at Alzheimer’s Research UK, commented on the findings. He acknowledged the disappointment when the original phase III studies failed to meet their primary outcomes, but highlighted that the subsequent analyses and the extension data provide encouraging evidence that treating earlier in the disease course may reveal benefits that were not detectable in broader patient groups. Dr Karran noted that while the observed improvements in people with mild symptoms are modest, the sustained effect over several years is the key observation that supports further study.
Dr Karran emphasized the need for longer and more targeted trials to confirm whether the benefits grow over time and to determine whether solanezumab can meaningfully alter disease progression. The final assessment, he said, will depend on whether the upcoming, more focused phase III trial reproduces these promising effects. Results from that trial were expected to be available in late 2016.
Source: Alzheimer’s Research UK
Image Credit: The image is in the public domain
Original Research: Findings will be presented at the Alzheimer’s Association International Conference 2015 in Washington, D.C., during the week of July 21, 2015.