Solanezumab
About Solanezumab
Solanezumab is an experimental, humanized antibody that binds to β-amyloid and is being investigated as a potential treatment to slow the progression of mild to moderate Alzheimer’s disease. One hypothesis regarding the cause of Alzheimer’s disease is that amyloid beta clumps together forming plaques on the brain which kill brain cells. Alzheimer’s disease is a chronic neurodegenerative disorder that results in a progressive decline in cognitive functions including memory, decision-making and language and ultimately leads to death. In short-term clinical studies, solanezumab appeared to have dose-dependent effects on amyloid beta in blood and cerebrospinal fluid. The clinical studies to date have been too short to evaluate any potential delay in the progress of Alzheimer’s disease. The only side effect experienced in clinical studies that appeared to be associated with solanezumab treatment has been mild chills consistent with an infusion reaction; other side effects reported in the Phase 2 study include nausea, vomiting, headache, back pain and cough. The drug is being developed by Eli Lilly.
How Solanezumab Works
Solanezumab binds to soluble ß-amyloid and thereby may draw the peptide away from the brain through the blood. This could reduce the formation of amyloid plaque seen in the brains of patients with Alzheimer’s disease and hypothesized to kill brain cells.
Clinical Trials
In May 2009, Eli Lilly announced that it had begun enrolling patients in two separate but identical Phase 3 clinical trials of solanezumab as a potential treatment to delay the progression of mild to moderate Alzheimer’s disease. The trials, called EXPEDITION and EXPEDITION 2, will each include a treatment period that lasts 18 months and are expected to enroll a total of 2,000 patients age 55 and over from 16 countries. The EXPEDITION clinical trials are identical multicenter, randomized, double-blind, placebo-controlled trials. Patients enrolled in the trials will be randomized in a 1:1 ratio (500 patients in each trial arm) to receive intravenous infusions of either placebo or 400 mg of solanezumab once every four weeks. Patients who are taking currently available symptomatic treatments for Alzheimer’s disease can continue treatment during their participation in the EXPEDITION trials. The primary objective of both trials is to test whether solanezumab will slow the cognitive and functional decline of Alzheimer’s disease patients as compared with placebo. These outcomes will be analyzed using measures of the Alzheimer’s Disease Assessment Scale-Cognitive subscore (ADAS-COG(11)), which measures cognitive function with an emphasis on memory and the Alzheimer’s Disease Cooperative Study – Activities of Daily Living scale (ADCS-ADL), which measures the ability to independently perform daily activities such as eating, bathing and using the telephone. Secondary objectives of the trials include different clinical benefits as measured by several brain-scanning and biochemical biomarkers and ratings scales and quality of life impact. EXPEDITION is being conducted in Argentina, Brazil, Canada, Japan and United States. EXPEDITION 2 is being conducted in Australia, France, Germany, Italy, Japan, Korea, Poland, Russia, Spain, Sweden, Taiwan, United Kingdom and United States.