Solanezumab fails in Phase 3: What do we know?

By December 6, 2016In the News

December 6, 2016

Joshua Grill, PhD, and Aimee Pierce, MD

screen-shot-2016-12-05-at-9-35-47-amThis week, at the Clinical Trials on Alzheimer’s Disease (CTAD) meeting in San Diego, we will likely learn more about the recent announcement from Eli Lilly and company that their Phase 3 clinical trial of the monoclonal antibody against the soluble form of beta amyloid, solanezumab, did not demonstrate adequate efficacy to pursue approval from the U.S. Food and Drug Administration. Until then, here is what we do know:

  • The drug solanezumab failed, but the trial didn’t. The purpose of the trial was to measure whether solanezumab was safe and effective enough for general use in people with mild Alzheimer’s dementia. The safety of the drug was previously shown in two very large clinical trials in people with mild-to-moderate Alzheimer’s dementia and the current results do not appear to change the safety profile of the drug. The efficacy of the drug, however, was not substantial enough to warrant use as a treatment.
  • The effect of this drug was never believed to be sizable (that is, the drug did not halt the progression of disease in any study) but it turns out that the effect was even smaller than believed. The objective of the trial was to measure whether long periods of treatment could slow disease progression, even slightly, and that end point was not achieved.
  • Several other anti-amyloid therapies are in development and this result should not reduce enthusiasm for those trials and those drugs. A clinical trial sets out to answer very specific questions. The specific question in the Lilly trial was “Is 18-months of treatment with solanezumab adequate to slow the rate of progression of Alzheimer’s disease in people with mild dementia?” Even though the answer was no, there are many important questions that remain to be answered, even some about solanezumab.
  • The amyloid hypothesis remains viable. The amyloid hypothesis posits that the accumulation of amyloid is the first step in a cascade of detrimental changes in the brain leading to Alzheimer’s disease.  There are varying forms of amyloid in the brain and the body and solanezumab only targeted one form. Other forms must be tested. Further, the true test of the amyloid hypothesis may only be to test these treatments in even earlier studies, such as those in people with Mild Cognitive Impairment or people with normal healthy memories, to see if reducing amyloid levels can delay or prevent the onset of dementia or memory problems entirely. These studies are underway and more are coming soon, including the Anti-Amyloid treatment in Asymptomatic Alzheimer’s disease (A4) study of solanezumab, which remains open to enrollment at UCI MIND.

Developing new treatments for Alzheimer’s disease is a difficult task. Despite this most recent set-back, this remains an exciting and promising time in the field and there are many additional on-going clinical trials of varying drugs, treating amyloid as well as other targets. The Lilly trial, while disappointing, is still an important step in our larger effort toward improved therapies for people with Alzheimer’s disease. The people who participated in this study should be proud of the important contribution they have made, though we all wish the outcome would have been different. We are grateful to them. We will continue to work with them and their families, and all families dealing with or concerned about Alzheimer’s disease, until we find effective treatments and preventions.