- For Print
- October 31, 2022
Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced today that it has received notification that Aricept® (donepezil hydrochloride), a treatment for Alzheimer’s disease and dementia with Lewy bodies that was discovered and developed in-house, has been granted Category 2* status based on the results of a reexamination of its efficacy, dosage and administration for the treatment of dementia with Lewy bodies (DLB) in Japan. In conjunction with this, Eisai plans to promptly submit an application for a partial change to label regarding dosage and administration. The indication for DLB remains unchanged.
The indication of "suppression of progression of dementia symptoms in DLB" was approved in September 2014, primarily based on a Phase II study (Study 431) and Phase III study (Study 341) conducted by Eisai on people living with DLB in Japan. In accordance with the condition for the approval of this indication, "a clinical trial to verify the efficacy and safety of the drug in patients with DLB should be conducted and the results of the trials and analyses should be submitted promptly after completion," Eisai conducted a post-marketing clinical study (Study 419) to evaluate the efficacy and safety of the drug in patients with DLB.
The results of Study 419 did not show a statistically significant difference between the placebo group and the Aricept group in the primary endpoint of global function (CIBIC-plus** comprehensive assessment), but the re-examination based on post-marketing studies, including the results of Study 419, stated that “at present, the evaluation of clinical function in DLB using CIBIC-Plus is not always sufficiently established as an evaluation method, and it is difficult to comprehensively evaluate the efficacy of this drug for DLB, although efficacy was seen in some patients. On the other hand, treatment with this drug showed a trend toward improvement in cognitive function (MMSE***), and this result is consistent with the results of the clinical trial at the time of approval of the drug. Since there are a certain number of patients who can be expected to benefit from the administration of this drug, it was concluded that the efficacy should be evaluated after the start of administration, and administration should only continue if efficacy is confirmed.”
Therefore, it was concluded that the approved label (dose and administration) and package insert should be appropriately revised (Category 2).
The condition of the approval was lifted as of the date of receipt of the reexamination results.
Along with this prompt application for a partial change to label regarding dosage and administration for the DLB indication, Eisai will place the highest priority on the provision of proper use and safety information for this drug, and will make continued contributions to address the diversified needs of, and increase the benefits provided to people living with DLB and their families.
Public Relations Department,
Eisai Co., Ltd.
[Notes to Editors]
- 1. Changes to the Aricept (donepezil hydrochloride) label for Dementia with Lewy bodies (planned application seeks to change underlined parts)
Dosage and Administration
*You can scroll to the left or right here
|Label Prior to Revision||Planned Contents of Application|
Suppression of progression of dementia symptoms in dementia with Lewy bodiesThe usual initial adult dose for oral use is 3 mg of donepezil hydrochloride once daily. After 1 to 2 weeks the dose is increased to 5 mg. The dose is increased to 10 mg after dosing at 5 mg for 4 or more weeks. The dose can be reduced to 5 mg according to patients' symptoms.
Suppression of progression of dementia symptoms in dementia with Lewy bodies
- 2. About Post-Marketing Clinical Study 419
Study 419 is a post-marketing clinical trial conducted in accordance with the condition of approval established at the time of the September 2014 approval of the indication for the suppression of progression of dementia symptoms in dementia with Lewy bodies (DLB). The study was conducted as a placebo-controlled, double-blind, parallel-group, randomized, study to evaluate the efficacy of 12 weeks of treatment with Aricept in 140 people living with DLB, with global function (CIBIC-plus comprehensive assessment) as the primary endpoint. In the Aricept group, 3 mg was administered once daily during weeks 1-2, 5 mg during weeks 3-6, and 10 mg during weeks 7-12. The results of the Study 419 did not show a statistically significant difference in efficacy between the placebo and Aricept groups at the time of the final analysis in the primary endpoint, the CIBIC-plus comprehensive assessment. Regarding safety, no new issues were observed in the frequency or severity of adverse events compared to those observed in previous clinical studies. In the reexamination, it was determined that the products efficacy for dementia symptoms in DLB is not completely negated by Study 419, and that some patients could be expected to benefit, considering the results on cognitive function (MMSE) in Studies 431 and 341 at the time of approval. The results of this study will be published in a future paper, etc.
* Category 2: Partial changes in approval (modifications in approved items as directed)
** CIBIC-plus (the Clinician's Interview-Based Impression of Change plus caregiver input): a validated clinical instrument used to measure change in global function through an interview with patients and their caregivers. Patients are evaluated by an assessor who is independent from the attending physician on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse and very much worse) in four major categories: General, Mental/Cognitive State, Behavior, and Activities of Daily Living.
*** MMSE (Mini-Mental State Examination): A method for assessing cognitive function. Comprised of the categories orientation, memorization, attention, calculation, recent and distant memory, comprehension, reading and writing, as well as design. Test scores range from 30 (normal) to 0 (severely impaired).