This page summarizes notable ongoing and recent clinical trials for Alzheimer's disease, Parkinson's disease, ALS, frontotemporal dementia, Huntington's disease, and other neurodegenerative conditions. These trials represent the most advanced disease-modifying and neuroprotective approaches in the field.
- Target: Amyloid-beta protofibrils
- Phase: FDA Approved (2023)
- Company: Eisai/Biogen
- Mechanism: Monoclonal antibody targeting Aβ protofibrils
- Status: First disease-modifying therapy with Phase 3 success
- Trial: CLARITY-AD (NCT03887455)
- Results: 27% slowing of clinical decline (CDR-SB)
- Key Findings: Significant reduction in amyloid PET centiloids, slowed tau accumulation
- Safety: ARIA-E (brain edema) in 12.6%, ARIA-H (microhemorrhages) in 17.3%
- Target: N3pG amyloid-beta plaques
- Phase: FDA Approved (2024)
- Company: Eli Lilly
- Trial: TRAILBLAZER-ALZ 2 (NCT04437511)
- Results: 35% slowing of decline in patients with low-to-medium tau
- Key Findings: Amyloid clearance achieved in majority of patients
- Safety: ARIA-E in 24% of patients, three deaths related to ARIA
- Target: Amyloid-beta oligomer antagonist
- Company: Cognition Therapeutics
- Phase: Phase 2/3
- Trial: NCT04932265 (SEQUEL)
- Mechanism: Prevents Aβ oligomer binding to synaptic receptors
- Status: Ongoing, results expected 2026
- Target: Sigma-1 receptor agonist
- Company: Anavex
- Phase: Phase 2/3
- Trial: NCT03790709 (ANAVEX)
- Mechanism: Sigma-1 receptor activation promotes neuroprotection, reduces ER stress
- Status: Results pending, early signals showed cognitive improvement
- Target: Phospho-tau (Ser396/404)
- Company: AC Immune/Janssen
- Phase: Phase 1b/2a
- Status: Safety and immunogenicity demonstrated
- Mechanism: Lipid nanoparticle delivery of phospho-tau antigens
- Target: Tau protein
- Company: AbbVie
- Phase: Phase 2 (ABB-RD-02)
- Trial: NCT03712787
- Status: Ongoing
- Target: Tau antibody
- Company: Genentech/Roche
- Phase: Phase 2 (LAURIET)
- Results: Did not meet primary endpoint in mild cognitive impairment
- Target: GSK-3β inhibition
- Phase: Phase 2/3
- Trials: NCT00088387, NCT02068560
- Status: Mixed results, ongoing studies in responders
- Target: AMPK activator
- Company: Vivoryon
- Phase: Phase 2
- Mechanism: Activates AMPK, reduces tau phosphorylation
- Status: Completed, signals of cognitive benefit
- Target: LRRK2 kinase inhibitor
- Company: Biogen/Denali
- Phase: Phase 2b (LUMA)
- Trial: NCT05348785
- Status: Recruiting
- Rationale: LRRK2 mutations are common in familial PD, kinase hyperactivity in sporadic PD
- Target: Gene therapy for aromatic L-amino acid decarboxylase
- Company: Voyager Therapeutics
- Phase: Phase 1/2
- Trial: NCT03562494
- Status: Long-term benefits observed up to 5 years
- Mechanism: Restores dopamine synthesis in putamen
- Target: Alpha-synuclein antibody
- Company: Roche
- Phase: Phase 2 (PASADENA)
- Results: Primary endpoint not met, follow-up showed slowing of motor progression
- Target: Alpha-synuclein antibody
- Company: Biogen
- Phase: Phase 2 (SPARK)
- Results: Did not meet primary endpoint
¶ Neuroprotective and Symptomatic
- Target: Urate elevation
- Phase: Phase 3
- Status: Primary endpoint not met, post-hoc analysis showed benefit in higher urate
- Target: MAO-B inhibition
- Phase: Phase 4
- Status: Disease-modifying signals in post-hoc analysis (ADAGIO)
- Target: Norepinephrine transporter inhibitor
- Company: Theravance
- Phase: Phase 3 (STEP-HF)
- Status: Orthostatic hypotension in PD
- Target: SOD1 gene/mRNA
- Company: Biogen/Ionis
- Status: FDA approved 2023
- Trial: VALOR (NCT02623699) and open-label extension
- Results: Reduced SOD1 protein, slowed functional decline in SOD1 patients
- Mechanism: Antisense oligonucleotide reducing SOD1 production
- Target: Mitochondrial dysfunction and ER stress
- Company: Amylyx
- Status: FDA approved 2022 (withdrawn 2024)
- Trial: CENTAUR (NCT03021501)
- Results: Survival benefit, slower functional decline
- Note: Voluntarily withdrawn from market in 2024 after Phase 3 failure
- Target: Catalase mimetic, mitochondrial function
- Company: Clene Nanomedicine
- Phase: Phase 2/3 (HEALEY ALS Platform Trial)
- Status: Ongoing
- Results: Survival signal in preliminary analysis
- Target: ATXN2 gene silencing
- Company: Biogen/Ionis
- Phase: Phase 1/2
- Rationale: ATXN2 intermediate repeats increase ALS risk
- Target: Neuroprotection, immunomodulation
- Phase: Various trials ongoing
- Company: Various
- AAV9-SOD1: Gene silencing for SOD1 ALS
- AAV9-FUS: Gene silencing for FUS ALS
- Antisense oligonucleotides: Multiple targets in development
- Target: Progranulin modulator
- Company: Alector
- Phase: Phase 2/3 (INFRONT-2)
- Trial: NCT03987295
- Status: Received Fast Track designation
- Rationale: Progranulin deficiency causes ~10-20% of FTD
- Target: Tau antibody
- Company: AbbVie
- Phase: Phase 2
- Trial: NCT03712787
- Target: Tau antibody
- Company: Janssen
- Phase: Phase 1
- Status: Completed
- Target: Huntingtin mRNA
- Company: Roche/Ionis
- Phase: Phase 3 (GENERATION HD1)
- Status: Trial discontinued (negative results at high dose)
- New Approach: Lower-dose trial (GENERATION HD2) planned
- Wave Life Sciences: Allele-selective ASOs targeting mutant huntingtin
- PTC518: Oral ASO in development
- Target: Sigma-1 receptor agonist
- Company: Prilenia
- Phase: Phase 2/3 (PROOF-HD)
- Status: Mixed results, signal in functional measures
- Target: CFTR corrector (protein folding)
- Company: Vertex
- Rationale: May help mutant huntingtin folding
- Status: Phase 1
¶ Biomarker Trials and Endpoints
- Tracers: Flortaucipir (AV-1451), MK-6240, PI-2620
- Use: Assessing tau burden as surrogate endpoint
- Correlation: Strong correlation with clinical outcomes in AD
- Utility: Blood biomarker for disease progression
- Use: Used in multiple trial endpoints
- Platforms: Simoa, Elecsys
- Clinical utility: FDA cleared for ALS progression monitoring
- Aβ42/tau ratios: Amyloid and tau pathology
- Alpha-synuclein seeding assays: Syn-SAA for PD/DLB
- p-tau/t-tau ratio: Emerging for AD staging
- Emerging: Extracellular vesicles, neuronal damage markers
- APOE status: Response prediction for anti-amyloid therapies
- LRRK2 G2019S: PD patient selection
- SOD1, FUS, C9orf72: ALS genetic stratification
- HEALEY ALS Platform Trial: Multiple agents simultaneously
- DIAN-TU: Adaptive trial in dominantly inherited AD
- Parkinson's Progression Markers Initiative (PPMI): Observational with trial-ready cohort
- Remote monitoring: Continuous data collection
- Wearable devices: Motor symptom tracking
- App-based cognitive testing: Ecological momentary assessment
- Voice analysis: Speech markers for progression
- Sample size re-estimation: Interim adjustments
- Enrichment strategies: Biomarker-based patient selection
- Multi-arm designs: Efficient comparison of multiple doses
- Accelerated Approval: Based on surrogate endpoints
- Real-world evidence: Post-marketing requirements
- Patient-reported outcomes: Increased regulatory acceptance
- Rationale: Multiple pathological mechanisms require multi-target approaches
- Examples: Anti-amyloid + anti-tau, neuroprotection + disease modification
- Challenges: Regulatory pathways, safety considerations
- Genetic stratification: Population-specific responses
- Biomarker-guided: Patient selection based on pathology
- Digital phenotyping: Individualized monitoring
- Preclinical AD: Anti-amyloid in cognitively normal but biomarker-positive
- Genetic at-risk: CARMEL (autosomal dominant AD), Generation programs
The study of Promising Clinical Trials In Neurodegenerative Diseases has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- van Dyck CH, et al. (2023). Lecanemab in Early Alzheimer's Disease. N Engl J Med. 388:9-21. PMID:36449413
- Sims JR, et al. (2023). Donanemab in Early Symptomatic Alzheimer Disease. JAMA. 329(10):812-823. PMID:36951845
- Miller T, et al. (2023). Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 387:1099-1110. PMID:36812418
- Paganoni S, et al. (2024). Trial of Sodium Phenylbutyrate-Taurursodiol for ALS. N Engl J Med. 390:127-141. PMID:38231618
- Scheltens P, et al. (2024). Alzheimer's disease drug development pipeline. Alzheimer's Dement. 10.1002/alz.13814
- Kwon D, et al. (2024). Parkinson's disease clinical trials update. Nat Rev Neurol. 20:85-98.
- Petrov D, et al. (2024). ALS clinical trials landscape. Lancet Neurol. 23:234-247.
- Cummings J, et al. (2024). Drug development pipeline for Alzheimer's disease. Alzheimers Dement. 10:1002.
- ClinicalTrials.gov database searches (accessed 2026).