Two emerging therapies for reducing the progression of dementia in Alzheimer's patients were the stars of the Alzheimer's Association International Conference 2018, namely Eisai Co. Ltd. and Biogen Inc.'s elenbecestat and Amgen Inc.'s experimental therapy AMG 520.
Elenbecestat helped achieve a 31% decrease in the rate of dementia progression in Alzheimer's disease patients, a clinically important marker of the midstage study, according to results released July 25 at the meeting. The main goal of the phase 2 trial, named Study 202, was to evaluate the drug's safety and how well patients tolerated it after 18 months of treatment. Elenbecestat is a beta-amyloid cleaving enzyme, or BACE, inhibitor. It works by blocking the action of BACE, which is vital to the production of beta-amyloid proteins that accumulate in the brain of Alzheimer's patients.
The two companies also released topline results for a separate Alzheimer's drug from another phase 2 trial, dubbed Study 201, showing that cognitive abilities of Alzheimer's patients receiving the highest dose of BAN2401 declined more slowly than those taking a placebo. Previously, a 12-month review of Study 201 failed to reach the milestones for success.
Amgen's investigational drug AMG 520, which is being developed through two phase 3 studies, also grabbed the attention of the audience at the conference, held in Chicago July 22-26. In order to decrease the duration of its trials, Amgen is enrolling patients with APOE4 gene variants, which puts patients at a higher risk of developing Alzheimer's disease.
Roche Holding AG presented data on two midstage trials of its Alzheimer's medicine crenezumab, which helps decrease amino acids that are typical of the disease. The drug is designed to bind to and promote the removal of neurotoxic oligomers.
A majority of the 98 patients in the ongoing phase 2 trials, named Abby and Blaze, showed lower levels of the so-called amyloid beta, or abeta, oligomers after being administered crenezumab. About 86% of the patients receiving the drug via an injection in their veins saw a 43% decline in the amino acid, while 89% of the patients receiving an injection under the skin saw a 48% decrease.
New York-based Anavex Life Sciences Corp. said its Alzheimer's disease drug Anavex 2-73 showed improvement in cognition and daily activities of patients in a midstage trial. The biopharmaceutical company's 57-week phase 2a study saw 80% of the patients improve scores on standard tests of cognition and activities of daily living.
Dementia risk in women
Elsewhere at the conference, studies presented showed how gender, reproductive history, pregnancy history, hormone therapy and verbal memory impact dementia and Alzheimer's disease in women.
Researchers reported that women with three or more children had a 12% lower risk of dementia compared to women with one child. They also found that each additional miscarriage was associated with a 9% rise in risk of dementia, compared to women who reported no miscarriages.
Women who experience their first menstrual period at 16 years or older were at 31% greater risk of Alzheimer's later in life, compared to those who had their first period at 13 years or younger. Additionally, women experiencing natural menopause at 45 years or younger were at 28% greater risk of dementia, compared to women who experience natural menopause after 45 years.
A separate study suggested that the number of months of pregnancy, particularly months spent in the first trimester, is a significant predictor of Alzheimer's risk. Researchers said women who spent 12.5% more months pregnant than other women had about 20% lower Alzheimer's risk.
Another study suggested that hormone therapy may not always be associated with cognitive harm. Researchers also found that women appeared to sustain their cognitive performance in early stages of the disease, compared to men despite having moderate levels of Alzheimer's disease.
Other results
A number of other studies were highlighted during the conference, including results that showed agitation improved significantly in Alzheimer's disease patients taking nabilone, a synthetic cannabinoid, compared to placebo.
In another study, insomnia drugs such as zolpidem, zopiclone and zaleplon, also known as Z-drugs, showed a 40% increased risk of any type of fracture, with risk increasing for those on higher doses. Another study related to insomnia found that a tailored lighting system could improve sleep, mood and behavior in Alzheimer's patients. Zolpidem is sold under the name Ambien and is marketed by Sanofi.