scholarly journals Disease-modifying effect of solanezumab evaluated by delayed-start analysis in a Japanese subpopulation with mild Alzheimer's disease

2017 ◽  
Vol 5 (5) ◽  
pp. 141-149
Author(s):  
Tomomi Nakamura ◽  
Shinji Fujikoshi ◽  
Jumpei Funai ◽  
Taka Matsumura
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Modifying Effect ◽  
Disease Modifying

DELAYED-START ANALYSES IN THE PHASE 3 SOLANEZUMAB EXPEDITION3 STUDY IN MILD ALZHEIMER’S DISEASE

2018 ◽  
pp. 1-7
Author(s):  
H. Liu-Seifert ◽  
M.G. Case ◽  
S.W. Andersen ◽  
K.C. Holdridge ◽  
P.S. Aisen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phase 3 ◽  
Significant Treatment ◽  
Treatment Difference ◽  
Significant Difference ◽  
Efficacy Measures ◽  
Modifying Effect ◽  
Disease Modifying ◽  
Significant Treatment Difference

OBJECTIVE: A delayed-start design has been proposed to assess a potential disease-modifying effect in investigational drugs for Alzheimer’s disease that target the underlying disease process. We extended this methodology to recently obtained data from the EXPEDITION3. METHODS: EXPEDITION3 was a Phase 3, double-blind study with participants randomized to solanezumab (400 mg) or placebo every 4 weeks for 80 weeks, with an optional extension of active treatment. The delayed-start analysis was designed to determine if a statistically significant treatment difference established during the placebo-controlled period is maintained (at predefined level) during the delayed-start period, which would suggest the active drug has a disease-modifying effect. The delayed-start analysis was assessed across multiple efficacy measures, and includes data from baseline in the placebo-controlled period and up to 9 months in the delayed-start period. RESULTS: No significant difference was observed between the placebo and solanezumab treatment groups at the end of the placebo-controlled period for the Alzheimer’s Disease Assessment Scale-Cognitive 14-item subscale. A significant treatment difference was observed at the end of the placebo-controlled period for the Alzheimer’s Disease Cooperative Study-Activities of Daily Living instrumental items, an effect also seen at 6 months in the delayed-start period, and the noninferiority criterion was met. No other efficacy measures met these criteria. CONCLUSIONS: Delayed-start statistical methodology was used to understand the longitudinal outcomes in EXPEDITION3 and its extension. The small treatment differences observed at the end of the placebo-controlled phase prevented adequate assessment of any putative disease modifying effect.

scholarly journals The Alzheimer’s Disease THErapy with NEuroaid II (ATHENE) Study: A Double-Blind Randomized Delayed-Start Trial to Assess the Safety and Efficacy of MLC901 (NeuroAiD™II) as an add-on Treatment to Cholinesterase Inhibitors or Memantine in Patients With Mild to Moderate Alzheimer's Disease

2021 ◽  
Author(s):  
Christopher Chen ◽  
Qingshu Liu ◽  
Rejesh Babu Moorakonda ◽  
Nagaendran Kandiah ◽  
Boon Yeow Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Events ◽  
Cognitive Assessment ◽  
Standard Treatment ◽  
Serious Adverse Events ◽  
Significant Difference ◽  
Early Starters ◽  
Modifying Effect ◽  
Disease Modifying

Abstract BackgroundPreclinical and clinical studies indicate a role for MLC901 (NeuroAiDTMII) in Alzheimer’s Disease (AD). We investigated its safety and efficacy as add-on therapy to standard treatment and evaluated a disease modifying effect in mild to moderate AD.MethodsMild-moderate probable AD patients by NINCDS-ADRDA criteria, stable on acetylcholinesterase inhibitors or memantine (n=125) were randomized to receive MLC901 (early starters) or placebo (delayed starters) for 6 months, followed by a further 6 months during which all patients received MLC901, in a delayed-start design. The primary outcome measure was serious adverse events at 6 months, secondary outcomes included the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) and other cognitive assessment scales.ResultsThere was no significant difference in the risk of serious adverse events between early and delayed starters at month (M) 6 (22.6% vs. 27.0%, risk difference = -4.4%, 90% CI -16.9 to 8.3%). Furthermore, there was no significant difference in the risk of adverse events, including the occurrence of stroke or vascular events, between early and delayed starters throughout the 12-month study period. The early-starters differed significantly on ADAS-Cog from the delayed-starters at M9 (mean difference -3.36, 95% CI -5.64 to -1.09) and M12 (mean difference -2.35, 95% CI -5.45 to 0.74). Other cognitive assessment scales showed trends in favor of MLC901.ConclusionsMLC901 is a safe adjunct to standard treatment for mild-moderate AD. There is no indication that the risk of any adverse events, including vascular, is increased with MLC901 in the study population. The cognitive outcomes provide support for a disease-modifying effect of MLC901 which requires confirmation in further studies. Clinical trial registration: ClinicalTrials.gov, NCT03038035. https://clinicaltrials.gov/ct2/show/NCT03038035

Measuring Disease Modification in Alzheimer's Disease

CNS Spectrums ◽  
2007 ◽  
Vol 12 (S1) ◽  
pp. 11-14
Author(s):  
Jeffrey L. Cummings
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immunoglobulin A ◽  
Disease Process ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Disease Modification ◽  
Amyloid Disease ◽  
Therapeutic Modalities ◽  
Disease Modifying

AbstractWe appear to be on the brink of a new epoch of treatment for Alzheimer's disease. Compelling evidence suggests that Aβ42 secretion is the triggering event in the pathogenesis of Alzheimer's disease, and that tau aggregation may be an important secondary event linked to neurodegeneration. Prophylactic administration of anti-amyloid agents designed to prevent Aβ accumulation in persons with subclinical disease is likely to be more effective than therapeutic interventions in established Alzheimer's disease. Drug development programs in Alzheimer's disease focus primarily on agents with anti-amyloid disease-modifying properties, and many different pharmacologic approaches to reducing amyloid pathology and tauopathy are being studied. Classes of therapeutic modalities currently in advanced-stage clinical trial testing include forms of immunotherapy (active β -amyloid immunoconjugate and human intravenous immunoglobulin), a γ-secretase inhibitor, the selective Aβ42-lowering agent R-flurbiprofen, and the anti-aggregation agent tramiprosate. Non-traditional dementia therapies such as the HMG-CoA reductase inhibitors (statins), valproate, and lithium are now being assessed for clinical benefit as anti-amyloid disease-modifying treatments. Positive findings of efficacy and safety from clinical studies are necessary but not sufficient to demonstrate that a drug has disease-modifying properties. Definitive proof of disease-modification requires evidence from validated animal models of Alzheimer's disease; rigorously controlled clinical trials showing a significantly improved, stabilized, or slowed rate of decline in cognitive and global function compared to placebo; and prospectively obtained evidence from surrogate biomarkers that the treatment resulted in measurable biological changes associated with the underlying disease process.

scholarly journals P2-298: Assessing the economic value of potential disease-modifying agents in Alzheimer's disease using simulation

2013 ◽  
Vol 9 ◽  
pp. P467-P467
Author(s):  
Denis Getsios ◽  
Shien Guo ◽  
Nikhil Revankar ◽  
Linus Jonsson ◽  
Peter Neumann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Economic Value ◽  
Disease Modifying ◽  
Disease Modifying Agents
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