Topline results released today by Eli Lilly and Company show that their eagerly awaited phase 3 EXPEDITION3 trial of the novel monoclonal antibody solanezumab failed to reach its primary endpoint of slowing cognitive decline in patients with mild dementia from Alzheimer's disease (AD).
The trial included more than 2100 participants from 11 countries, with roughly half randomly assigned to 400 mg of solanezumab administered intravenously every 4 weeks for 74 weeks and the other half receiving matching placebo. Results at the 80-week follow-up showed no significant difference in AD Assessment Scale-Cognitive subscale (ADAS-Cog14) scores between the two groups (P = .095).
"While the study results, including many secondary clinical endpoints, directionally favored solanezumab, the magnitudes of treatment differences were small," the company said in a statement. They added that there are no plans for further pursuit of regulatory approval for the drug for this specific patient population.
"The Alzheimer's Association is sad and disappointed by the negative results of this trial," Maria Carrillo, PhD, chief science officer of the organization, told Medscape Medical News.
"But this doesn't mean that we should stop other trials that are going on and looking at antiamyloid treatments," she said. "Also, there was a slight hint that there was a benefit with solanezumab. So would looking at the disease earlier have given a better chance of a larger efficacy? We don't know the answers."
While questions remain about what the next steps may be regarding further development of the drug, the company notes that it will work with the investigators to conclude the EXPEDITION, EXPEDITION2, and EXPEDITION3 open-label extensions "appropriately."
Solanezumab is still being studied in other ongoing trials, including as a potential therapy for patients with mild cognitive impairment due to AD in EXPEDITION-PRO, in patients with preclinical AD in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) trial, and in the Dominantly Inherited Alzheimer's Disease (DIAN) trial.
As reported by Medscape Medical News, original analysis of the phase 3 EXPEDITION1 and EXPEDITION2 studies did not show significant benefit of 400 mg infusions of solanezumab vs placebo in patients with mild to moderate AD.
However, prespecified secondary analysis in the first trial showed a reduction in cognitive decline in the subgroup with mild AD. These reductions were not significant in secondary analysis of the second trial. However, pooled data showed a significant 34% reduction in cognitive decline, as shown on the ADAS-Cog14.
Expectations were high for EXPEDITON3, the first phase 3 study to assess only patients with mild dementia due to AD, according to the company.
"This was a good example of what we would consider a 'next-generation trial' that used an enrichment strategy to make sure everyone had amyloid or at least the protein that you're trying to treat. So there was a lot of hope," said Dr Carrillo.
"For so many years, many of our clinical trials had perhaps 25% to 30% of people not having Alzheimer's-type dementia, but another type of dementia. So we learned a lot from EXPEDITION1 and 2," she added.
However, the results "were not what we had hoped for and we are disappointed for the millions of people waiting for potential disease-modifying treatment for Alzheimer's disease," said president and CEO of Lilly, John C. Lechleiter, PhD, in the statement.
The company will present further trial results at the Clinical Trials on AD meeting in San Diego, California, on December 8 at 6:15 pm PT, and the presentation will be broadcast live via webcast.
Medscape Medical News © 2016 WebMD, LLC
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Cite this: EXPEDITION3 Topline Results: Solanezumab Doesn't Meet Primary Endpoint in AD Dementia - Medscape - Nov 23, 2016.