Clinical Trials

Date: 2016-12-08

Type of information: Results

phase: 3

Announcement: presentation of results at the 9th Clinical Trials on Alzheimer's Disease (CTAD) meeting

Company: Eli Lilly (USA - IN)

Product: solanezumab

Action mechanism:

• monoclonal antibody. Solanezumab is Lilly's Phase 3 monoclonal antibody being studied as a potential therapy for patients with mild Alzheimer's disease. Solanezumab binds to soluble monomeric forms of amyloid-beta after it is produced, allowing it to be cleared before it clumps together to form beta-amyloid plaques.

Disease: Alzheimer's disease

Therapeutic area: Neurodegenerative diseases

Country: Australia, Canada, France, Germany, Italy, Japan, Poland, Spain, Sweden, UK, USA

Trial details:

• EXPEDITION3 is a multinational, phase 3 trial of solanezumab in more than 2,100 patients diagnosed with mild dementia due to Alzheimer's disease. The study includes an 18-month placebo-controlled period followed by an open label extension. Enrollment was completed in 2015 and the last patient visit for the placebo-controlled period occurred in October 2016. EXPEDITION3 is the first phase 3 trial to evaluate only people with mild dementia due to Alzheimer's disease. (NCT01900665)

Latest news:

• • On December 8, 2016, Eli Lilly presented detailed results of its phase 3 EXPEDITION3 trial at the 9th Clinical Trials on Alzheimer's Disease (CTAD) meeting. As previously disclosed, solanezumab did not meet the primary endpoint in the study initiated in people with mild dementia due to Alzheimer's disease, and Lilly will not pursue regulatory submissions for solanezumab for the treatment of mild dementia due to AD.
• While the study results, including many secondary clinical endpoints, directionally favored solanezumab, the magnitudes of treatment differences were small.
• Primary Endpoint: Patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo. This finding represented an 11 percent reduction in decline (p=.095), as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog14) subscale. The ADAS-Cog14 measures a person's cognitive functions, including memory, attention and language abilities.
• Key Secondary Clinical Endpoints: As the primary endpoint was not met in this study, the p-values for the efficacy secondary statistical analyses were not adjusted for multiple comparisons.
• Patients treated with solanezumab had a 13 percent slowing of cognitive decline (p=0.014) compared to patients treated with placebo as measured by the Mini-Mental State Examination (MMSE). The MMSE is the most commonly used test for complaints of problems with memory or other mental abilities and can be used by clinicians to help diagnose dementia and to help assess its progression and severity. It consists of a series of questions and tests, each of which scores points if answered correctly. The MMSE tests a number of different mental abilities, including a person's memory, attention and language.
• The Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale showed a 15 percent slowing in decline (p=0.004) between patients treated with solanezumab and patients treated with placebo. The CDR-SB scale measures cognitive and functional performance — in areas such as memory, orientation and personal care — through semi-structured interviews of patients and their family members or other reliable informants.
• Patients treated with solanezumab had a slowing of decline in complex activities of daily living compared to patients treated with placebo. This finding represented a 14 percent slowing of decline (p=.019) as measured by the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living (ADCS-iADL). The ADCS-iADL scale measures a person's independent performance in complex activities of daily living such as participating in a conversation, preparing a meal or shopping.
• A different functional measure, the FAQ (Functional Activities Questionnaire), did not show a statistically significant difference between patients treated with solanezumab and patients treated with placebo (7 percent reduction in decline, p=0.140). The FAQ scale is a different informant-based measure of functional abilities. Informants provide performance ratings of the patient on ten complex higher-order activities.
• Biomarkers: Changes in plasma a-beta were similar to those seen in previous studies, and the differences between treatment and placebo groups were statistically significant. Changes in amyloid deposition as measured by positron emission tomography (PET) imaging did not reach statistical significance between treatment and placebo groups.
• Adverse events: Events more frequent in the solanezumab treatment group that were statistically significant include: spinal osteoarthritis (1.1 percent in the solanezumab group, 0.4 percent in the placebo group), dysuria (0.9 percent in the solanezumab group, 0.2 percent in the placebo group), vitamin D deficiency (1.4 percent in the solanezumab group, 0.6 percent in the placebo group), and nasal congestion (1.2 percent in the solanezumab group, 0.4 percent in the placebo group). The incidence of vasogenic edema (ARIA-E or amyloid-related imaging abnormality-edema/effusions) was approximately 0.1 percent of patients treated with solanezumab and 0.3 percent of patients on placebo.
• • On November 23, 2016, Eli Lilly announced that solanezumab did not meet the primary endpoint in the EXPEDITION3 clinical trial, in people with mild dementia due to Alzheimer's disease. Patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo (p=.095), as measured by the ADAS-Cog14 (Alzheimer's Disease Assessment Scale-Cognitive subscale). While the study results, including many secondary clinical endpoints, directionally favored solanezumab, the magnitudes of treatment differences were small. There were no new safety signals identified in the study. Lilly will not pursue regulatory submissions for solanezumab for the treatment of mild dementia due to Alzheimer's disease. Lilly will work with investigators to appropriately conclude the open-label extensions for EXPEDITION, EXPEDITION2 and EXPEDITION3. The next steps for the remaining elements of the solanezumab development program have not yet been determined.
• The EXPEDITION3 study outcome is expected to result in a fourth-quarter charge of approximately $150 million (pre-tax), or approximately $0.09 per share (after-tax).

 

Is general: Yes