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ºÚÁÏÍø., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “ºÚÁÏÍø”) announced today that its anti-Alzheimer's agent Aricept® (donepezil hydrochloride) has received approval for a new indication for dementia with Lewy bodies (DLB) in Japan. This marks the first time a treatment has been approved for DLB anywhere in the world.

DLB was discovered by Dr. Kenji Kosaka, Professor Emeritus of Yokohama City University. DLB is considered to be one of Japan's three major types of dementia, alongside Alzheimer's disease and vascular dementia. According to a number of reports, DLB affects between 4.3% (based on epidemiology) and 41.4% (based on autopsies) of elderly patients with dementia in Japan^1,2, with the number of patients increasing due to the aging of the population. It is pointed out that DLB is difficult to be diagnosed because the disease presents characteristic symptoms such as cognitive fluctuations, visual hallucinations and parkinsonism in addition to progressive cognitive impairment. Moreover, the development of a new treatment option has been desired by patients and medical communities, as there had been approved medication available to treat DLB.

The new indication approval was primarily based on a Phase Ⅱ study (Study 431) and a Phase Ⅲ study (Study 341) conducted by ºÚÁÏÍø on patients with DLB in Japan. Also, in accordance with the conditions of approval, ºÚÁÏÍø will work after launch to ensure that an observational study is carried out to gather data on long-term use and an additional clinical trial is performed to confirm efficacy and also promote the appropriate use of Aricept for this additional indication. The registration validity period for Aricept for this indication is 4 years.

Through this additional indication of Aricept for the treatment of DLB, ºÚÁÏÍø will ensure and provide information of diagnosis, treatment and care of DLB and contribute to improvement the quality of life of patients. As the originator of Aricept, ºÚÁÏÍø strives for making further contribution to the improvement of treatment and care as well as increasing public awareness towards the disease.

DLB is a degenerative form of dementia discovered in Japan that is pathologically characterized by decreased neurons in the brain and brainstem and the appearance of vast numbers of Lewy bodies. In neurochemistry, DLB is characterized by a loss of acetylcholine-producing neurons in the brain similar to that seen in patients with Alzheimer's disease. In addition to obligatory symptoms associated with progressive cognitive impairment, the disease also presents with behavioral and neuropsychiatric symptoms, motor disturbances, and dysautonomia. Of these, cognitive fluctuations, visual hallucinations and idiopathic parkinsonism have a high rate of incidence and are considered to be core symptoms of the disease³. In Japan, DLB constitutes one of the three major types of dementia diagnosed, alongside Alzheimer's disease and vascular dementia, affecting between 4.3% (based on epidemiology) to 41.4% (based on autopsy) of elderly patients with dementia, according to various studies^1,2.

In an exploratory Phase Ⅱ study (Study 431) of Aricept in Japanese patients with DLB, Aricept demonstrated significant improvement over placebo in core efficacy outcome measures such as cognitive function, behavioral and neuropsychiatric symptoms, and global function.
Based on the positive results of Study 431, ºÚÁÏÍø conducted a Phase Ⅲ study (Study 341) to assess the superiority of 12-week Aricept treatment over placebo in patients with DLB. The co-primary endpoints set for Study 341 were cognitive function and behavioral and neuropsychiatric symptoms. In addition, the safety and efficacy of long-term Aricept administration (52 weeks) were also investigated. Based on the results of Study 341, the expected objective of simultaneous improvement in both cognitive function as well as behavioral and neuropsychiatric symptoms was not achieved. Regarding cognitive function, statistically significant improvement was observed in the Aricept 10mg group compared to the placebo group at the final evaluation point after 12 weeks of treatment, and cognitive function was also observed to be maintained at a level higher than at baseline after 52 weeks of treatment. On the other hand, improved behavioral and neuropsychiatric symptoms were observed in all treatment groups, both Aricept and placebo, and suggested no statistically significant difference among groups at the final evaluation point after 12 weeks of treatment.
From a combined analysis of the results of Study 431 and Study 341 up to and including Week 12, the most common adverse events (AEs) observed to have occurred more frequently in the Aricept group compared to the placebo group (incidence rate greater than 3% in either treatment arm) were parkinsonism, elevated blood creatine phosphokinase, increased blood pressure, diarrhea and anorexia, and the results were consistent with the drug's safety profile as reported in patients with Alzheimer's disease. Regarding AEs related to symptoms of parkinsonism, which occurred more often than it does in patients treated with Aricept for Alzheimer's disease, no large difference in the Aricept groups was reported, with all AEs being mild or moderate and nonserious. Furthermore, no notable difference in the incidence of AEs during the extended treatment period was found, suggesting that delayed AE onset induced by the long-term administration was unlikely to appear.
The results of both Study 431⁴ and Study 341⁵ have since been published in scientific papers and presented at academic conferences, respectively.