Solanezumab slightly slows Alzheimer's disease, investigators report

By John Murphy, MDLinx
Published January 5, 2016

Key Takeaways

Researchers announced results of the first drug to apparently slow the progression of underlying disease, not just the symptoms, in patients with mild Alzheimer’s. The results were modest, but statistically significant.

The drug, solanezumab, is an anti-amyloid antibody developed by Eli Lilly. It is intended to bind to amyloid-beta in the brain and then clear it out before the amyloid-beta can clump into amyloid plaques that interfere with neurons. These latest results showed that solanezumab achieved statistically significant reductions in cognitive and functional declines in patients with mild Alzheimer’s disease who were started earlier and treated longer when compared with similar patients who were started later and treated for a shorter period.

The drug’s investigators presented their findings at Alzheimer's Association International Conference 2015 (AAIC) in Washington, DC, and simultaneously published their study in Alzheimer’s & Dementia: Translational Research & Clinical Investigations.

These results are actually an extension of two prior phase III clinical trials (the EXPEDITION studies), released in 2012, in which solanezumab failed to meet clinical endpoints of cognitive or functional improvements.

In this new extension analysis, investigators took a second look at the original data but only in patients who had mild dementia at the beginning of the study. All of these patients were randomized to the same active treatment—intravenous solanezumab 400 mg every 4 weeks—but starting at different times, which resulted in two treatment groups: early-start and delayed-start. The patients in the delayed-start group first received placebo for 18 months before being switched into active treatment for 2 years.

The analysis showed that patients who were on therapy longer (the early-start group) showed less cognitive and functional decline than those who started later (the delayed-start group). Both groups continued to decline, but the early-start group progressed somewhat less.

“Starting therapy early is important, [in] that you will be modifying underlying disease in a way that accrues benefit with time. So that the earlier you start, the greater the benefit. And if you start later, you don’t ‘catch up,’” said study co-author Paul Aisen, MD, director of the Alzheimer's Therapeutic Research Institute at the University of Southern California in San Diego, who presented the results at AAIC.

This is the first clinical trial in Alzheimer’s research to use the delayed-start methodology.

But methodologies and analyses are one thing, and clinical differences in individual Alzheimer’s patients—remembering where the car keys are, or what day of the week it is—are another.

Solanezumab did show modest and sustained improvement on scales of cognition (ADASCog14) and function (ADCS-iADL) in early-start patients, but not in measures of dementia and cognitive impairment (MMSE and CDR-SB). "The lack of statistically significant results on the MMSE and CDR-SB scales warrants some caution in drawing firm conclusions from these analyses," the authors wrote.

Dr. Aisen addressed this distinction at an AAIC question and answer session: “We see in the solanezumab program, in mild subjects, roughly a one-third slowing of [functional] decline. So, in mild subjects, the slowing…is more modest. In moderate subjects, it becomes greater.” He reiterated that the earlier and longer the treatment, the larger the benefit. But “slowing the rate of progression of disease by one-third, which is apparently what occurred in mild subjects with solanezumab, is an important change on the long-term trajectory—on the long term history—of the impact of the disease.”

He also noted that solanezumab was safe and well tolerated with no significant adverse effects. The drug’s investigators aim to release definitive and final results of their analysis in 2016.

On a related note, other investigators on the same Q&A panel predicted that there will be no single “silver bullet” drug for Alzheimer’s disease that pinpoints only one factor, such as amyloid-beta. Rather, the successful treatment for Alzheimer’s will likely be a combination or “cocktail” of treatments that target not only amyloid-beta, but also tau, and perhaps other yet unknown causes.

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