Solanezumab – Another monoclonal antibody reaches Phase III

Contributed by: David Geldmacher, M.D., Medical Director of the Memory Disorders Clinic at the University of Virginia.

On May 21, Eli Lilly and Co. announced that a Phase III Trial of their agent solanezumab, also known as LY2062430, would begin enrollment.

In Lilly’s Phase III program, a total of 2000 patients with mild to moderate AD are expected to receive either a 400 mg infusion of solanezumab or a placebo once every four weeks. Each research volunteer will participate over about 19 months. The overall trial is anticipated to be completed in mid 2012.

On first pass, this agent would appear to be similar to bapineuzumab which is already in Phase III trials being carried out by Elan and Wyeth. There are molecular differences between the two monoclonal antibody lines, which suggest that solanezumab acts primarily outside the brain to sequester soluble amyloid beta peptide in the peripheral circulation. If true, this would predict a lower risk for toxic events in the brain, like the vasogenic edema (brain swelling) reported in Elan’s Phase II trials.

On the other hand, a site of action outside the central nervous system might mean lower overall potency. Given the small absolute effects seen with bapineuzumab in its Phase II trial, lower potency would not bode well for solanezumab’s effectiveness. Of course, all anti-amyloid immnunotherapies depend a great deal on the validity of the amyloid hypothesis.

At a practical level, participants in the solanezumab trial will receive infusions every four weeks instead of the quarterly regimen for bapineuzumab. This will triple the risk for infusion related complications, and places a higher burden on patients. If approved under their current regimens, costs of drug administration would also likely favor the agent requiring the fewest number of infusions. However, a dramatically greater effectiveness would go a long way to off-setting increased treatment costs.


  1. As I understand it, Solanezumab works by drawing SOLUBLE A-Beta away from the brain, binding the protein with a monoclonal antibody designed to target it. Thus it may not reduce plaques already formed, but may hinder the soluble A-Beta (including 'oligomers' - dimers, trimers, etc. of amyloid-beta) - preventing these free-floating proteins from interfering with synaptic communication/ transmission - is this correct?

  2. Actually, by removing the soluble beta-amyloid out of the brain, it is thought that beta-amyloid plaques will begin to release oligomers that can be removed as well. The time that it takes for plaque break-down to occur will be much longer than the removal of the soluble form.
    Michael Rafii, MD, PhD