First Regulatory Approval for DLB Treatment Comes from Japan | Lewy Body Dementia Association LBDA

First Regulatory Approval for DLB Treatment Comes from Japan

Donepezil (brand name Aricept) has received approval in Japan for the treatment of dementia with Lewy bodies (DLB). This is the first time a treatment has been approved for DLB anywhere in the world, demonstrating significant research progress in clinical and scientific measures needed for DLB clinical trials. The study provided important validation of the importance of cholinesterase inhibitors in the treatment of DLB.

The Donepezil-DLB Study Investigators group represented 48 specialty centers and was led by Dr. Etsuro Mori of Tohoku University and colleagues, including Dr. Kenji Kosaka who first discovered DLB in the 1980’s. A clinical trial Phase II study evaluated safety and efficacy of donepezil at different dosages in individuals with DLB, while the Phase III study measured efficacy of the drug at two dosages. The randomized, double-blind, placebo controlled studies led to the regulatory approval.

In the Phase II trial, 140 individuals with DLB were divided into 4 groups receiving either placebo, 3mg, 5 mg, or 10 mg of donepezil for 12 weeks, resulting in improvement in cognition and behavior for those who received donepezil. Delusions, hallucinations and cognitive fluctuations were lower in those receiving donepezil over placebo. 108 patients continued in the open label phase of the trial, which demonstrated improved or maintained cognitive function at 52 weeks compared to placebo.

Adverse events compared to placebo were consistent with the drug’s safety profile for patients with Alzheimer’s disease; all adverse effects were rated as mild or moderate and non-serious and only 8% of the cohort withdrew from the study due to side effects. Gastrointestinal side effects were more common for those who received donepezil; one side effect, parkinsonism, occurred more in those with DLB than Alzheimer’s.

In the Phase III trial (currently in press) 142 individuals with DLB were randomly assigned to placebo, 5 mg or 10 mg donepezil daily for 12 weeks. Those on 10 mg donepezil significantly improved over the placebo group. 110 patients continued in the open label phase of the study and received 10 mg donepezil daily. 100 subjects completed the study and cognitive function improvement was maintained for 52 weeks. Adverse events were similar to the Phase II study, with gastrointestinal symptoms most common. Individuals were permitted to reduce their dose from 10 mg to 5 mg if adverse effects were bothersome. Parkinsonism occurred in 5% of the participants.

In conclusion, donepezil was found to be safe and effective in treating dementia with Lewy bodies, providing improving and maintaining cognitive function for at least 1 year. Compared to studies of donepezil in Alzheimer’s disease, individuals with DLB may receive benefits from treatment with the drug twice as long as those with Alzheimer’s disease.

Until now, the only regulatory approval for any form of Lewy body dementia is Exelon, which is approved to treat cognition in Parkinson’s disease dementia.

Source: *4 Mori E, Ikeda M, Kosaka K. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol 2012; 72: 41-52. *5 Ikeda M, Mori E, Kosaka K. A clinical Phase III study of Donepezil in dementia with Lewy bodies (preliminary report): observations from a study integrating a placebo-controlled, double-blind trial and long-term administration. The 29th Annual Meeting of the Japanese Psychogeriatric Society 2014.

This study was supported by Eisai Pharmaceuticals.