🧠 Alzheimer's Disease Therapeutic Vaccine Tracker
Comprehensive tracking of Alzheimer's disease therapeutic vaccine development targeting amyloid-beta plaques, tau protein tangles, and neuroinflammation. Alzheimer's affects 7 million Americans, 55 million globally. Immunotherapy approaches aim to slow cognitive decline by clearing pathological proteins. Multiple Phase 2/3 trials underway targeting Alzheimer's pathology. Active and passive immunization strategies show promise but face safety challenges after early failures (AN1792).
⚠️ MAJOR UNMET MEDICAL NEED:
Alzheimer's disease affects 7 million Americans, 55 million globally. Leading cause of dementia and 6th leading cause of death in US. $345 billion annual cost in US alone. No disease-modifying treatments available - current drugs only temporarily manage symptoms. Therapeutic vaccines represent hope for slowing/preventing cognitive decline.
Alzheimer's Vaccines by Development Phase
7M
US Cases (55M Globally)
12
Vaccines in Development
🔬 Phase 3 Clinical Trial
Target
Pathological tau protein
Phase 2 Results
Safe, reduced tau pathology
Trial Status
ADAMANT Phase 3 ongoing
Details: AADvac1 is first tau-targeted vaccine in Phase 3. Synthetic peptide vaccine inducing antibodies against pathological tau (misfolded, phosphorylated). Unlike amyloid-beta approach, tau pathology correlates better with cognitive decline. Phase 2 (ADAMANT study, 196 patients) showed excellent safety, high antibody response rates (>90%), reduced tau pathology biomarkers (CSF p-tau decline), slowed cognitive decline trend. Phase 3 ADAMANT trial enrolling ~500 mild Alzheimer's patients. Monthly injections for 2+ years. Primary endpoint: cognitive function (ADAS-Cog). Secondary: brain atrophy, tau PET imaging. Results expected 2025-2026. If successful, could be first approved Alzheimer's therapeutic vaccine.
🧬 Phase 2 Clinical Trials
Target
Amyloid-beta (Aβ1-14)
Phase 1/2a Results
Safe, good antibody response
Description: UB-311 synthetic peptide vaccine targeting N-terminal Aβ (amino acids 1-14) linked to carrier protein. Designed to avoid T-cell activation that caused meningoencephalitis in AN1792. Phase 1/2a showed safety, robust antibody responses, biomarker improvements (CSF Aβ42 increase). Phase 2b ongoing in mild Alzheimer's. Subcutaneous injection every 3 months. Aims for disease-modifying effect by clearing amyloid plaques.
Technology
Aβ1-15 in liposomes
Phase 1b Results
Safe, promising biomarkers
Description: ACI-24 Aβ1-15 peptide formulated in liposomes as adjuvant. Targets amyloid aggregates. Phase 1b (prodromal/mild AD) showed good safety, antibody responses, CSF biomarker improvements. Phase 2 evaluating efficacy. Quarterly injections. Partnership with Janssen accelerating development.
🧪 Phase 1 & Preclinical Development
Candidates: (1) Lu AF20513 (Lundbeck) - Active Aβ vaccine with novel adjuvant; (2) ACI-35 (AC Immune/Eli Lilly) - Tau vaccine targeting pS396/pS404; (3) DNA vaccine platforms - Plasmid DNA encoding Aβ/tau epitopes.
Approaches: (1) mRNA vaccines - Encoding Aβ/tau antigens for immune response; (2) Nanoparticle vaccines - Enhanced antigen delivery to immune cells; (3) Combination vaccines - Targeting both Aβ AND tau simultaneously; (4) Anti-inflammatory vaccines - Targeting neuroinflammation (TNF-α, IL-1β).
⚠️ Discontinued/Failed Programs - Learning from Setbacks
AN1792 (Elan/Wyeth): First Aβ vaccine. Phase 2 halted 2002 after 6% developed meningoencephalitis (brain inflammation from T-cell activation). Despite termination, long-term follow-up showed plaque reduction in responders but NO cognitive benefit. Key lesson: Avoid T-cell epitopes, target B-cell responses only.
Bapineuzumab (Passive Immunization): Monoclonal antibody based on AN1792 approach. Phase 3 failed - no efficacy, vasogenic edema (ARIA-E) in ApoE4 carriers. Reinforced challenges of amyloid hypothesis.
📊 Disease Burden & Future Outlook
Alzheimer's Disease Burden: 7 million Americans, 55 million globally. Projected to reach 13 million US cases by 2050. Leading cause of dementia (60-80% of cases). 6th leading cause of death in US. $345 billion annual US cost (projected $1 trillion by 2050). No cure available - current drugs (cholinesterase inhibitors, memantine) only manage symptoms temporarily. New anti-amyloid antibodies (aducanumab, lecanemab) show modest benefit but high cost, limited access, safety concerns (ARIA).
Therapeutic Vaccine Strategy: Active immunization aims for long-lasting immunity with less frequent dosing vs. passive antibodies requiring frequent infusions. Potential advantages: lower cost, better accessibility, sustained response. Challenges: safety (AN1792 lesson), efficacy (amyloid hypothesis questioned), timing (early intervention critical).
Future Directions: Tau vaccines most promising (better correlation with symptoms). Combination approaches (amyloid + tau). Precision medicine (biomarker-guided, genetic risk stratification). Prevention trials in pre-symptomatic stage. Success requires understanding disease heterogeneity, patient selection, appropriate endpoints.