The Alzheimer's Pipeline After Semaglutide: Who's Still in the Race

The semaglutide failure changes the landscape

On March 19, 2026, Novo Nordisk presented full data from the EVOKE and EVOKE+ trials at the AD/PD International Conference. Oral semaglutide — the blockbuster GLP-1 drug that transformed diabetes and obesity treatment — showed no clinical benefit in early Alzheimer's disease. Both trials missed their primary endpoint (CDR-SB at 104 weeks) and their secondary endpoint (ADCS-ADL-MCI). A pooled analysis found no delay in progression from mild cognitive impairment to mild Alzheimer's (Science, Mar 2026).

The trials enrolled approximately 3,800 patients over two years. Semaglutide did reduce CSF biomarkers of Alzheimer's pathology (p-tau181) by roughly 10%, but the effect was too small to translate into meaningful cognitive benefit (The Lancet, Mar 2026).

But the Alzheimer's pipeline itself is far from empty. Here's what the ClinicalTrials.gov data shows right now.

The numbers

There are 260 active Alzheimer's disease trials on ClinicalTrials.gov. Of those, 156 are actively recruiting and 31 are in Phase 3.

That last number is the most striking. Only 66 of the 260 active Alzheimer's trials are industry-sponsored. The rest are run by academic medical centers and government agencies. In obesity, the pipeline is overwhelmingly industry-driven. In Alzheimer's, the opposite is true — academic research still dominates.

That imbalance reflects the disease's history: decades of expensive Phase 3 failures drove many large pharma companies out of neuroscience entirely. The companies still investing in Alzheimer's are making a high-conviction bet.

Who leads Phase 3

With Novo Nordisk's semaglutide program effectively concluded, the Phase 3 recruiting landscape is led by a name you might not expect: Bristol-Myers Squibb, through its 2024 acquisition of Karuna Therapeutics.

BMS/Karuna's 8 Phase 3 trials are all studying KarXT (xanomeline-trospium), a muscarinic receptor agonist. Five trials (ADAGIO-1, -2, and -3) target agitation in Alzheimer's dementia. Three more (MINDSET-1 and -2) are studying cognitive impairment. This is a different approach from the amyloid-clearing antibodies that have dominated the space — KarXT targets symptoms through cholinergic signaling rather than trying to clear the underlying pathology.

The full active pipeline

Beyond Phase 3, the broader Alzheimer's pipeline is mostly academic. Here are the top sponsors by total active trial count across all phases.

Academic institutions hold 5 of the top 10 sponsor positions. This is unusual — in most high-value therapeutic areas (obesity, oncology), industry sponsors dominate the leaderboard. In Alzheimer's, academic medical centers are still the backbone of the clinical pipeline.

The three industry bets still standing

For BD and competitive intelligence teams, the active Alzheimer's pipeline now comes down to three distinct therapeutic strategies.

1. Anti-amyloid antibodies (Lilly, Roche)

Eli Lilly's donanemab (Kisunla), approved in 2024, is the current standard alongside Eisai/Biogen's lecanemab (Leqembi). Lilly has 6 active Alzheimer's trials including two Phase 3 studies (TRAILBLAZER-ALZ 3 in preclinical Alzheimer's and TRAILBLAZER-ALZ 5 in early symptomatic patients). They also have two new Phase 1 compounds in early Alzheimer's — likely next-generation antibodies including remternetug, which has Phase 3 data expected around Q2 2026 (NeurologyLive, 2026). Notably, 88.5% of remternetug injections in early trials were self-administered at home, a significant convenience advantage over infusion-center antibodies.

Roche has 6 active trials including 3 in Phase 3, continuing their long-running investment in the amyloid and tau hypotheses after the failures of gantenerumab and crenezumab.

2. Muscarinic agonists / symptom management (BMS/Karuna, Axsome)

BMS/Karuna's KarXT targets the muscarinic receptor system. Rather than trying to clear amyloid plaques, it aims to improve cholinergic signaling — addressing agitation, psychosis, and cognitive symptoms directly. With 8 Phase 3 trials, this is the largest active Alzheimer's clinical program by any single sponsor.

Axsome Therapeutics' AXS-05 (dextromethorphan-bupropion) is another symptomatic approach targeting Alzheimer's agitation, with an FDA decision expected in April 2026. If approved, it would join aducanumab, lecanemab, and donanemab as one of the few drugs specifically indicated for Alzheimer's.

3. The next wave — beyond amyloid and cholinergic

The early-phase pipeline (35 Phase 2 trials and 18 Phase 1 trials) includes mechanisms that go well beyond the amyloid hypothesis: anti-tau antibodies, neuroinflammation modulators, mitochondrial targets, and epigenetic approaches. Many of these are academic-led, which means they could become licensing targets for pharma companies looking to rebuild their neuroscience portfolios.

What BD teams should be watching

• BMS/Karuna KarXT readouts. With 8 Phase 3 trials running, expect a wave of data in 2026-2027. Success would validate the muscarinic approach and could trigger a rush of symptomatic treatment programs from competitors.
• Lilly's remternetug Phase 3 data (Q2 2026). If the next-generation anti-amyloid antibody shows improved efficacy or convenience over donanemab, it reshapes the disease-modification competitive landscape.
• Axsome AXS-05 FDA decision (April 2026). An approval for Alzheimer's agitation would be a significant commercial milestone and validate symptomatic treatment as a viable market.
• Academic Phase 2 programs. With 75% of the pipeline academic-led, the next licensing opportunity is more likely to come from Washington University or Johns Hopkins than from a biotech startup. Track the Phase 2 completions.
• The GLP-1-in-neurodegeneration thesis is not dead. Semaglutide failed, but other companies may try different GLP-1 agonists, higher doses, or combination approaches. Watch for new IND filings in the next 6-12 months.