Eli Lilly said Monday that top-line results from the Phase II/III DIAN-TU study indicate that its investigational anti-amyloid monoclonal antibody solanezumab did not meet the primary endpoint of slowing cognitive decline versus matching placebo in patients at risk for, or who already have, dominantly inherited Alzheimer's disease. While additional analyses of secondary goals and biomarkers are ongoing and will be presented at the Advances in Alzheimer's and Parkinson's Therapies (AAT-AD/PD) focus meeting in April, Eli Lilly stated that it "does not plan to pursue a submission for solanezumab in people with dominantly inherited Alzheimer's disease…based on the result of the primary endpoint."
Chief scientific officer Daniel Skovronsky said "we look forward to the opportunity to analyse the data so that we may continue to propel the science forward and bring hope to these patients." The study, which was established in 2010 and sponsored by Washington University School of Medicine, tested solanezumab as well as Roche's gantenerumab, an IgG1 monoclonal antibody designed to bind to aggregated forms of beta-amyloid, against matching placebos to see if either could slow the rate of cognitive decline and improve disease-related biomarkers in patients with mutations causing dominantly inherited Alzheimer's disease. The primary goal is the DIAN Multivariate Cognitive Endpoint, a novel outcome measure designed to assess cognitive performance in patients with autosomal dominant Alzheimer's disease.
The news coincides with Roche announcing Monday that gantenerumab had also failed to achieve the study's main goal.
According to Eli Lilly, the primary efficacy analysis included 50 patients in the study who were randomly assigned to receive solanezumab and another 40 participants who got a matching placebo. The minimum four-year treatment period was completed by 36 solanezumab-treated patients. The drugmaker noted that the initial solanezumab dose was 400 mg every four weeks, although a late amendment to the study boosted the strength, resulting in approximately 25% of the total doses being administered at the 1600-mg level.
Commenting on the news, Mizuho Securities Vamil Divan remarked "we were not optimistic on this trial given it was a relatively small trial and in a more severe form of the disease." Meanwhile, Eli Lilly said the DIAN-TU study failure does not impact the ongoing A4 trial of solanezumab in older individuals who have evidence of amyloid in their brains, but do not show symptoms of memory impairment.
In 2016, Eli Lilly reported that solanezumab had failed to meet the primary endpoint of the Phase III EXPEDITION3 study in patients with mild dementia due to Alzheimer's disease. More recently, CEO David Ricks indicated that the company had no plans to re-analyse data from that trial, in light of Biogen and Eisai deciding late last year to resurrect their anti-amyloid beta antibody aducanumab after they had taken another look at results from two previously-shelved trials. Biogen CEO Michel Vounatsos said recently that his company plans to complete a US regulatory filing for aducanumab "as soon as possible."
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