The Alzheimer's drug development pipeline has reached unprecedented diversity in 2025, with 88 different clinical trials currently recruiting patients across multiple therapeutic approaches, marking a significant evolution beyond the traditional focus on anti-amyloid antibodies like aducanumab, lecanemab, and donanemab.
According to the latest annual analysis by Dr. Jeffrey Cummings and colleagues, published in Alzheimer's & Dementia: Translational Research and Clinical Interventions, twelve Phase 3 trials are expected to deliver results this year, spanning disease-modifying treatments, symptomatic therapies, and innovative medical devices.
Disease-Modifying Approaches Show Mixed Results
The small molecule drug landscape has experienced both setbacks and continued momentum. Alzheon's ALZ-801, designed to prevent beta-amyloid plaque formation, failed to meet its primary goal in a Phase 3 trial targeting people with early Alzheimer's and two copies of ApoE4. While some modest benefits were observed in participants with mild cognitive impairment (MCI), the trial was not designed to confirm efficacy in this subgroup.
In contrast, Novo Nordisk's semaglutide (Ozempic, Wegovy) represents one of the most anticipated developments, with two large Phase 3 trials each enrolling 1,840 participants for early Alzheimer's. The GLP-1 agonist, already proven effective for diabetes and weight management, is being tested based on early studies suggesting potential protection against Alzheimer's and other forms of dementia. Results are expected by the end of 2025.
Annovis Bio has launched a new 18-month, 750-person Phase 3 trial for buntanetap after disappointing initial results, focusing on a subgroup that showed potential positive effects. Results from this refined approach are expected in 2028.
Biologics Gain Momentum with Vaccines and Cell Therapies
The biologics sector is experiencing significant growth, with multiple vaccine trials underway. AC Immune SA and Takeda are testing beta-amyloid vaccine ACI-24.060 for Alzheimer's prevention in cognitively healthy individuals at risk and people with Down syndrome, with trials continuing through 2026.
GemVax/Kael Bio's GV1001, originally developed as a cancer vaccine, is now being tested for moderate-to-severe Alzheimer's in a Phase 3 trial in South Korea, expected to finish in 2028. Additionally, AC Immune SA and Janssen announced plans for a tau vaccine, JNJ-2056, for Alzheimer's prevention, with a Phase 2b trial in planning stages.
Cell therapy approaches are also advancing, with NK Gen Biotech's troculeucel (formerly SNK01) showing promise in early trials. Derived from patients' own "natural killer" immune cells, this infusion-based treatment launched a 36-person Phase 2 trial expected to conclude at the end of 2025, following positive data from three participants in a Phase 1 trial.
Innovative Drug Delivery Shows Promise
Roche's trontinemab represents a breakthrough in drug delivery, using a "Trojan Horse" approach to trick the blood-brain barrier and enable easier brain penetration. The anti-amyloid drug can be administered at lower doses and clears beta-amyloid plaques faster than existing treatments. Data from a 114-person Phase 1/2 trial showed substantially lower rates of ARIA (amyloid-related imaging abnormalities) compared to Leqembi and Kisunla, potentially offering a safer profile if results hold up in Phase 3 trials.
Symptomatic Treatments Target Multiple Domains
Beyond disease modification, numerous trials are addressing Alzheimer's symptoms. Karuna Therapeutics is testing KarXT, the first new schizophrenia drug approved in the US since the 1950s, in two Phase 3 trials for Alzheimer's-related psychosis, with results expected in 2025 and 2026 from trials involving 380 and 400 participants respectively.
For cognitive symptoms, an ongoing 348-person trial in Italy is exploring whether combining rotigotine (a Parkinson's drug affecting dopamine levels) with an already-approved cholinesterase drug can improve cognition in people with mild to moderate Alzheimer's.
Medical Devices Enter the Therapeutic Arena
Novel medical device approaches are showing early promise. Cognito Therapeutics' brain-stimulating light-and-sound headset, SPECTRIS, demonstrated lasting effects on brain volume and daily functioning in preliminary studies. A 670-person Phase 3 trial is ongoing, with safety and efficacy results expected by mid-2026.
Sinaptica Therapeutics is using repetitive transcranial magnetic stimulation (rTMS) to target specific brain regions. In a 48-participant Phase 2 trial, the rTMS protocol slowed cognitive decline over one year by just over 1 point on an 18-point scale, with Phase 3 trials planned.
The current pipeline represents a fundamental shift from the historically narrow focus on amyloid-targeting therapies to a more comprehensive approach addressing multiple pathways and symptom domains. With results from multiple Phase 3 trials expected throughout 2025, this year may prove pivotal in determining which therapeutic strategies will advance to market and provide new options for the millions affected by Alzheimer's disease.
