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AD Clinical Trials: Background and Update

AD Clinical Trials: Background and Update. Navneet Ramesh Renous Meeting 2 /10/ 14. Clinical Trials. Currently about 100 recruiting clinical trials Required for testing of new therapeutic options Limited by: Funding E thical considerations Strict patient requirements.

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AD Clinical Trials: Background and Update

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  1. AD Clinical Trials: Background and Update Navneet Ramesh Renous Meeting 2/10/14

  2. Clinical Trials • Currently about 100 recruiting clinical trials • Required for testing of new therapeutic options • Limited by: • Funding • Ethical considerations • Strict patient requirements

  3. Common Misconceptions • “There are already plenty of volunteers. They don't need me to participate.” • “If there is a clinical trial that could help me, my doctor will tell me about it.” • “If I join a clinical trial, I won't receive the same quality of care that I currently have with my doctor.” Alz.org

  4. Recent/Upcoming Clinical Trials • Solanezumab • Bapineuzumab • MK-8931 • NAV4694 • Encenicline • ACI-35

  5. Solanezumab • Monoclonal antibody that targets soluble amyloid-beta • Preclinical studies in mice showed reduced deposition of amyloid beta in the brain • Phase 1 & 2 clinical trials showed benefit in some AD patients

  6. Solanezumab– Phase 3 trials • Expedition 1 & Expedition 2 • Patients had mild-moderate AD • Permitted to take AChE inhibitors • Around 1000 patients in each • 500 received the drug • Consistent patient characteristics • About 70 percent of the patients completed the trial

  7. SolanezumabTrial Results • No significant reduction of amyloid-beta compared to placebo • No differences in tau or p-tau in CSF • Hippocampal volumes decreased in both placebo and treatment group • NOT found to have a benefit

  8. Bapineuzumab • Monoclonal antibody that targets fibrillar, oligomeric, and monomeric forms of Aβ • Reduced the amount of Aβ in the brain and improved memory in transgenic mice that overproduced Aβ • Reduced Aβ and tau in mild-moderate AD patients in Phase 2 clinical studies

  9. Bapineuzumab – Phase 2 Trials • Trial 1: APOE ε4 carriers • 1,200 participants; ~700 received drug • Trial 2: APOE ε4 NON-carriers • 1,331 participants; ~800 received drug • 2007-2012 • About 70 percent of the patients completed the trial

  10. BapineuzumabTrial Results • No significant reduction of amyloid-beta compared to placebo • Slight decrease in tau for APOE ε4 carriers • Antibody may affect cerebral arterioles • NOT found to have a benefit Salloway S et al. N Engl J Med 2014;370:322-333.

  11. MK-8931 • Aβ precursor protein site-cleaving enzyme (BACE) inhibitor • Entering Phase 2/3 trials • Phase 1 trials showed reduction in Aβ • Safety concerns

  12. NAV4694 Trial • NavideaBiopharmaceuticals • Amyloid-beta marker for PET scans • Fluorine-18 labeled precision • Phase 2b trial: • “NAV4694 produced high-quality diagnostic images that segregated MCI subjects into two discrete groups: amyloid-positive or amyloid-negative” • Low nonspecific binding

  13. Encenicline • Currently in Phase 3 Clinical Trial • Agonist of the α7 receptor found on certain hippocampal and cortical neurons in the brain • Works as a co-agonist with acetylcholine to potentiate the response of α7 receptors • α7 receptors: activated brain networks associated with sensory gating, attention and cognition • Improves neural processing and cognitive performance (ie. memory and executive function)

  14. Tau-Targeted Therapies • ACI-35: Vaccine against phosphorylated tau • Phase 1 trial • Also testing vaccine against amyloid (ACI-24 ) • Phase 1/2 trial • TPI 287 • abeotaxane (ie. taxoid) that stabilizes microtubules • Readily crosses blood brain barrier • Phase 1

  15. Summary • Amyloid beta may not be the best therapeutic target • Difficult to assess differences due to genetics • Focus on early diagnosis and treatment options • Exciting trials are upcoming!

  16. Sources • http://online.wsj.com/article/PR-CO-20140206-910104.html • http://www.nejm.org/doi/full/10.1056/NEJMoa1312889#t=articleTop • http://www.nejm.org/doi/full/10.1056/NEJMoa1304839#t=articleTop • http://www.bizjournals.com/boston/blog/bioflash/2014/01/dunsires-new-biotech-envivo-takes.html?page=all • http://www.envivopharma.com/news-item.php?id=48 • http://globenewswire.com/news-release/2014/01/21/603701/10064872/en/Cortice-Announces-Enrollment-of-a-Clinical-Trial-Targeting-Tau-Dysfunction-in-Mild-to-Moderate-Alzheimer-s-Disease.html

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