E-2814
- Generic Name
- E-2814
European Regulators Reject Eli Lilly's Alzheimer's Drug Kisunla Over Safety Concerns
• The European Medicines Agency's advisory committee has recommended against approving Eli Lilly's Alzheimer's treatment Kisunla, citing safety concerns related to brain swelling.
• European regulators determined that the risks of amyloid-related imaging abnormalities (ARIA) outweigh the potential benefits of the drug, creating a notable divergence from US regulatory decisions.
• This rejection marks another instance where European and American regulators have reached different conclusions on new Alzheimer's treatments, highlighting regional differences in benefit-risk assessment.
Landmark Prevention Trial Launches to Stop Alzheimer's Before Symptoms Begin in Young Adults
• WashU Medicine initiates groundbreaking international trial testing Eli Lilly's remternetug in young adults as young as 18, targeting Alzheimer's prevention up to 25 years before expected symptom onset.
• The Primary Prevention Trial will enroll 240 participants from families with genetic mutations, focusing on removing or preventing amyloid beta plaques before cognitive symptoms develop.
• The $130 million study represents a collaborative effort between academic institutions, pharmaceutical industry, and foundations, with support from NIH, Alzheimer's Association, and private donors.
Key Neurology Advances of 2024: From Novel Therapies to Trial Innovations
• Donanemab's enhanced titration method significantly reduces ARIA-E frequency and severity while maintaining amyloid reduction in Alzheimer's patients.
• Liraglutide demonstrates neuroprotective effects against Alzheimer's disease dementia, highlighting the potential of GLP-1 analogues in AD treatment.
• Tolebrutinib shows promise in slowing disability progression in non-relapsing secondary progressive multiple sclerosis patients in the HERCULES trial.
Alzheimer's Disease Pipeline Shows Promise with 120+ Therapies in Development
• Over 120 Alzheimer's Disease treatment therapies are under development by 110+ companies globally, ranging from preclinical to marketed phases.
• Emerging therapies like NRDN-201, ST-501, and KarXT are in various clinical trial phases, showing potential for significant market impact.
• MapLight Therapeutics initiated a Phase 1 trial for ML-007/PAC, targeting schizophrenia and Alzheimer's disease psychosis, with Phase 2 trials planned.
• The FDA granted conventional approval to Leqembi (lecanemab-irmb), marking the first amyloid beta-directed antibody to transition from accelerated approval.
UCB's Bepranemab Shows Promise in Reducing Tau Tangles in Alzheimer's Subgroup
• Bepranemab, a monoclonal antibody from UCB Pharma, is the first to demonstrate a slowing of tau tangle accumulation in Alzheimer's patients, marking a potential shift in treatment strategies.
• Phase 2 trial data suggests cognitive benefits in a subgroup with low baseline tau levels and without the ApoE4 mutation, indicating a targeted approach may be necessary for efficacy.
• The trial results support the hypothesis that extracellular tau 'seeds' drive Alzheimer's progression, opening avenues for understanding disease mechanisms and developing combination therapies.
• Several companies are developing antibodies targeting the microtubule binding region (MTBR) of tau, with ongoing trials exploring their impact on tau spread and clinical outcomes.
Alzheimer's Clinical Trial Update: New Data on Tau-Targeting Drugs and More
• Eisai presented Phase 1/2 data on E2814, an anti-tau drug, showing reduced levels of disease biomarkers in participants with mild to moderate genetic Alzheimer’s.
• Roche terminated its agreement with UCB for beprenemab, an experimental tau-targeting antibody, after Phase 2 trial results showed it did not slow cognitive decline.
• A Phase 2 trial of intranasal insulin and empagliflozin showed that insulin alone was associated with a small improvement in cognitive test performance in early Alzheimer’s patients.
CTAD 2024: Mixed Results for Alzheimer's Therapies Highlighted
• Eisai's E2814, an anti-tau drug, showed promise in reducing disease biomarkers in a Phase 1 trial involving participants with genetic Alzheimer's, warranting further studies.
• Roche's trontinemab demonstrated effective amyloid reduction at high doses with a lower incidence of ARIA compared to other anti-amyloid antibodies in a Phase 1/2 trial.
• UCB's beprenemab, a tau-targeting antibody, failed to slow cognitive decline in a Phase 2 trial, leading Roche to terminate their development and commercialization agreement.
• Gene therapy LX001 from Lexeo Therapeutics showed early signs of success by increasing ApoE2 protein production and stabilizing amyloid levels in an ongoing Phase 1/2 study.
Alzheimer's Disease Therapeutics: Donanemab Dosing, Anti-Tau Antibody E2814, and Combination Intranasal Insulin/Empagliflozin Show Promise
• Enhanced titration dosing of donanemab in the TRAILBLAZER-ALZ-6 trial significantly reduced the frequency and severity of ARIA-E in early symptomatic Alzheimer's disease patients.
• Phase 1b/2 study data of E2814, an anti-tau therapeutic antibody, demonstrated a significant impact on early and late tau biomarkers in patients with dominantly inherited Alzheimer's disease.
• A phase 2 trial showed that combination treatment with intranasal insulin and empagliflozin improved cognition and modulated immune/inflammatory biomarkers in mild cognitive impairment or early Alzheimer's disease.
Eisai's Anti-MTBR Tau Antibody E2814 Shows Promise in Early Alzheimer's Disease
• Eisai's E2814, an anti-MTBR tau antibody, demonstrated significant reductions in CSF MTBR-tau243 and p-tau217 levels in patients with Dominantly Inherited Alzheimer's Disease (DIAD).
• Tau PET imaging suggested that E2814 stabilized or reduced brain tau accumulation in DIAD subjects, indicating potential inhibition of tau propagation.
• Eisai has initiated a Phase II clinical study (Study 202) to evaluate the safety and biomarker efficacy of E2814 in early Alzheimer's disease patients receiving lecanemab.
• The Phase II study will assess E2814's impact on early AD patients already on lecanemab therapy, with plans to expand the study to Japan.
Eisai's Anti-MTBR Tau Antibody E2814 Shows Promise in Alzheimer's Disease
• Eisai's E2814, an anti-MTBR tau antibody, demonstrated significant reductions in CSF MTBR-tau243 and p-tau217 levels in patients with Dominantly Inherited Alzheimer's Disease (DIAD).
• Brain tau accumulation, as observed by tau PET, stabilized or trended towards decrease in DIAD subjects administered E2814, suggesting inhibition of tau propagation.
• Eisai has initiated a Phase II clinical study (Study 202) to evaluate the safety, tolerability, and biomarker efficacy of E2814 in early Alzheimer's disease patients receiving lecanemab.
• The Phase II study will be a placebo-controlled, double-blind, parallel-group, dose exploration study, evaluating the safety, tolerability, and biomarker efficacy of E2814.
Drug Development Updates
Stay informed with timely notifications on clinical trials, regulatory changes, and research advancements related to this medication.
© Copyright 2025. All Rights Reserved by MedPath