BPS-034 (BPDO-1603 / DM Duo): A Comprehensive Analysis of a Fixed-Dose Combination for Alzheimer's Disease

1. Executive Summary

[BPS-034, also identified by the development code BPDO-1603 and marketed in South Korea as DM Duo, is an oral fixed-dose combination (FDC) medication developed by Hyundai Pharmaceutical Co., Ltd. for the treatment of moderate-to-severe Alzheimer's disease (AD). This report provides a comprehensive analysis of BPS-034, synthesizing available data on its pharmacology, clinical development, formulation, regulatory status, and safety profile.]

[The drug combines two established therapeutic agents: donepezil hydrochloride, an acetylcholinesterase inhibitor, and memantine hydrochloride, an N-methyl-D-aspartate (NMDA) receptor antagonist. This dual mechanism targets both the cholinergic deficit and glutamatergic excitotoxicity implicated in AD pathogenesis. The primary rationale for developing this FDC is to improve patient compliance and convenience by reducing pill burden, particularly as memantine is often dosed twice daily when administered separately, while donepezil is once daily.]

[The clinical development program for BPS-034 included a Phase 1 pharmacokinetic study (NCT05804279) in healthy adults, which likely finalized the formulation based on safety and bioavailability, following earlier bioequivalence studies. The pivotal Phase 3 trial (NCT04229927) evaluated the efficacy and safety of BPS-034 against donepezil monotherapy in patients with moderate-to-severe AD already stabilized on donepezil. This trial did not demonstrate statistical superiority of the combination over donepezil alone on its primary cognitive (Severe Impairment Battery - SIB) and global (Clinician's Interview-Based Impression of Change-plus - CIBIC-Plus) endpoints.]