Several DMTs are being investigated

There are currently several DMTs under investigation.¹ As of 2023, 44% of DMTs under investigation were biologics and 56% were small molecules.¹ 29% of the agents target neurotransmitters (including cognitive enhancers, and drugs being developed to reduce NPS), 17% target inflammation, 16% amyloid, 13% synaptic plasticity/neuroprotection, 9% tau, 7% metabolism and bioenergetics, 5% oxidative stress, and 3% proteostasis/proteinopathy.¹ DMTs make up 67% of all Phase 3 agents, 85% of Phase 2 agents, and 81% of Phase 1 agents.¹

The success of aducanumab and lecanemab suggests that understanding the biology of AD has progressed to identify targets that can slow cognitive decline following modulation.¹ Additionally, improvements in identification of drug targets, availability of informative biomarkers, identification of candidate drugs with promising pharmacokinetic and pharmacodynamic characteristics, better defined trial populations, and improved trial conduct, have all strengthened drug discovery.⁷

References:
1. Cummings J, Zhou Y, Lee G, et al. Alzheimer’s disease drug development pipeline: 2023. Alzheimers Dement (N Y) 2023; 9 (2): e12385.

2. Budd Haeberlein S, Aisen PS, Barkhof F, et al. Two randomized Phase 3 studies of aducanumab in early Alzheimer’s disease. J Prev Alzheimers Dis 2022; 9 (2): 197–210.

3. van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med 2023; 388 (1): 9–21.

4. Rashad A, Rasool A, Shaheryar M, et al. Donanemab for Alzheimer’s disease: a systematic review of clinical trials. Healthcare (Basel) 2023; 11 (1): 32.

5. Cummings J, Feldman HH, Scheltens P. The “rights” of precision drug development for Alzheimer’s disease. Alzheimers Res Ther 2019; 11 (1): 76.