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Drug Development.

Aishwarya Prasad1, Anshu Arora1, Arun Arora1

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Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
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Cholinesterase inhibitors (AChEIs) showed greater efficacy than monoclonal antibodies (mAbs) in improving Alzheimer's disease (AD) symptoms, despite mAbs being studied for longer durations. Further research is needed for direct comparison.

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Area of Science:

  • Neurology
  • Pharmacology
  • Clinical Research

Background:

  • Existing Alzheimer's disease (AD) research indicates modest benefits from monoclonal antibodies (mAbs) compared to cholinesterase inhibitors (AChEIs).
  • Direct comparative efficacy data between mAbs and AChEIs are limited.
  • This study aims to compare the efficacy of these drug classes using available evidence.

Purpose of the Study:

  • To compare the efficacy of monoclonal antibodies (mAbs) and cholinesterase inhibitors (AChEIs) in treating Alzheimer's disease.
  • To analyze risk-benefit profiles of these drug classes based on FDA data.
  • To evaluate AD drug efficacy using the ADAS-Cog scale.

Main Methods:

  • Efficacy data from FDA archives (through October 2024) were analyzed.
  • Five medications (donanemab, lecanemab, aducanumab, donepezil, galantamine) involving 11,122 subjects were included.
  • Drugs evaluated using the ADAS-Cog scale were selected; memantine was excluded due to differing outcome measures.

Main Results:

  • Cholinesterase inhibitors (AChEIs) demonstrated a mean difference of -2.82 on the ADAS-Cog scale versus placebo over 25.5 weeks.
  • Monoclonal antibodies (mAbs) showed a mean difference of -1.08 on the ADAS-Cog scale versus placebo over 77.3 weeks.
  • All analyzed drugs showed statistically significant improvements compared to placebo.

Conclusions:

  • While both drug classes showed statistically significant efficacy, AChEIs were approved for moderate to severe AD, and mAbs for mild cognitive impairment or mild dementia.
  • Differences in ADAS-Cog scale versions (e.g., ADAS-Cog 11 vs. 13) complicate direct efficacy comparisons.
  • Further research is necessary to definitively assess the comparative efficacy of newer mAbs against placebo and existing treatments.