Jan 25, 2018

Alzheimer’s Drug Solanezumab Fails in Phase 3 Clinical Trial

Researchers report that solanezumab, a treatment for Alzheimer's disease developed by Eli Lilly, did not significantly slow cognitive decline.


by Alzheimer's Reading Room

Solanezumab, a monoclonal antibody-based treatment for Alzheimer’s disease that targets amyloid plaques, did not significantly slow cognitive decline. The findings were published in the New England Journal of Medicine.

The hypothesis here was that if the drug could eliminate the soluble amyloid beta protein in the brain of Alzheimer's patients the progression of Alzheimer's disease might be stopped, or at least, slowed down.






  • Researchers have proposed that Alzheimer’s disease is caused by the buildup of a sticky protein called beta-amyloid.
  • According to this “amyloid hypothesis,” the protein forms plaques in the brain that damage and eventually destroy brain cells.
  • Solanezumab was designed to reduce the level of soluble amyloid molecules before they aggregate.
  • A total of 2,129 patients with mild dementia due to Alzheimer’s disease participated in the double-blind, placebo-controlled, phase 3 multicenter trial. 
This study was the first major Alzheimer’s clinical trial to require molecular evidence of amyloid deposition in the brain for enrollment. While the treatment did have some favorable effects, in the main measure of outcome — measured with a cognitive test called the Alzheimer’s Disease Assessment Scale-cognitive subscale — the researchers did not observe any statistically significant benefit compared with placebo.


The authors suggest that while it is not certain that this particular strategy or drug could be effective, it is possible that either not enough drug was administered or that the drug needs to be administered earlier in the disease course.

In other studies ongoing at Columbia University Irving Medical Center and other centers, solanezumab is being evaluated in presymptomatic patients at risk of Alzheimer’s disease. Other Alzheimer’s drugs are also in development and being tested at higher doses.

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“Although we are disappointed that this particular drug did not prove successful, the field is benefiting from each study,” says lead author Lawrence Honig, MD, PhD, professor of neurology at CUIMC. “There is hope that one of the newer ongoing studies may result in an effective treatment for slowing the course of Alzheimer’s disease.”

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The “amyloid hypothesis” began with a simple observation: Alzheimer’s patients have an unusual buildup of the protein amyloid in their brains. Thus, drugs that prevent or remove the amyloid should slow the onset of dementia. Yet all drugs targeting amyloid—including solanezumab from Eli Lilly and bapineuzumab from Pfizer and Johnson & Johnson, to add a few more high-profile flameouts to the fail pile—have not worked so far. Source the Atlantic

This is sure to disappoint researchers who have been hanging onto the “amyloid hypothesis” of Alzheimer’s — the notion that amyloid-beta accumulating in the brain is what drives the disease. Researchers at Lilly were among those believers, because even in the two previously failed trials, a subgroup of patients whose symptoms were mild did show some improvement while taking the drug. Source Forbes

Citation

The study is titled “Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease.”
N Engl J Med 2018; 378:321-330
DOI: 10.1056/NEJMoa1705971

Additional authors are Bruno Vellas, MD, Michael Woodward, MD, Merc. Boada, MD, PhD, Roger Bullock, MD, Michael Borrie, MB, ChB., Klaus Hager, MD, Niels Andreasen, MD, PhD, Elio Scarpini, MD, Hong Liu‑Seifert, PhD, Michael Case, MS, Robert A. Dean, MD, PhD, Ann Hake, MD, Karen Sundell, BS, Vicki Poole Hoffmann, PharmD, Christopher Carlson, PhD, Rashna Khanna, MD, Mark Mintun, MD, Ronald DeMattos, PhD, Katherine J. Selzler, PhD, and Eric Siemers, MD. Their affiliations are listed in the appendix of the paper.

The study was designed and funded by Eli Lilly and Company.