Eisai Inc. and Pfizer Inc [NYSE: PFE] announced today that the U.S. Food and Drug Administration (FDA) approved a new once-daily, higher-dose Aricept (donepezil HCl) 23 mg tablet for the treatment of moderate-to-severe Alzheimer's disease (AD). Aricept 23 mg tablet offers another dosing option for patients with moderate-to-severe AD, for whom few treatments are available. According to the Alzheimer's Association, approximately 3.6 million Americans age 65 and older have moderate-to-severe AD.
“We have a long-standing commitment to the AD community and recognize that there are few treatment options available”
The approval of Aricept 23 mg tablet is based on data from a large head-to-head study of Aricept 23 mg tablet versus Aricept 10 mg tablet in over 1,400 patients with moderate-to-severe AD. Two co-primary endpoints were examined: the Severe Impairment Battery (SIB), a validated clinical instrument that measures cognition, and the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC+), another validated clinical instrument that measures global function. Aricept 23 mg tablet demonstrated a statistically significant improvement in cognition, but did not achieve statistically significant improvement in global function, as compared to Aricept 10 mg tablet.
"Slowing the decline of cognitive symptoms is important at all stages of Alzheimer's disease," said Dr. Martin R. Farlow, professor and vice-chairman of research, department of neurology, Indiana University School of Medicine and lead author of the pivotal study publication. "Throughout the course of AD, caregivers are usually the first to notice changes in cognition. It's important for families to talk with their doctor when they notice a worsening in cognitive function in their loved ones to reevaluate therapeutic needs."
Based on the approved label, the recommended starting dose of Aricept is 5 mg once daily and can be increased to Aricept 10 mg once daily after four-to-six weeks. Moderate-to-severe AD patients who are established on a regimen of Aricept 10 mg tablet for at least three months are candidates for dose escalation to Aricept 23 mg tablet.
Nausea, vomiting, diarrhea and anorexia were the most common adverse events noted in the pivotal study of Aricept 23 mg tablet.
"We have a long-standing commitment to the AD community and recognize that there are few treatment options available," said Lonnel Coats, president and CEO, Eisai Inc. "In drawing upon our heritage, we are proud to offer a new dosing option to caregivers and patients living with this debilitating condition."
AD is a progressive, neurodegenerative disease. Age is the biggest risk factor for AD, as the chances of developing the disease double every five years after age 65. According to the Alzheimer's Association, by 2050 it is estimated 13.5 million Americans may have AD, and 77 percent - or 10.4 million - of them may have moderate or severe disease.
"With the growing aging population and the increasing burden of Alzheimer's disease on patients and their families, it is more important than ever to develop valuable therapies for the treatment of the disease," said Adele M. Gulfo, president and general manager, U.S. Primary Care Business Unit at Pfizer. "The approval of Aricept 23 mg tablet demonstrates our ongoing commitment to delivering treatment options that may help patients and their families living with Alzheimer's disease."
The head-to-head, double-blind, placebo-controlled, parallel-group clinical study randomized 1,467 patients with moderate-to-severe AD who had been treated for three months or more with Aricept 10 mg tablet. In the study, patients who received the increased dose of Aricept 23 mg tablet once daily were compared to patients who continued on with the Aricept 10 mg tablet once daily to determine if Aricept 23 mg tablet could offer incremental benefit in cognition (SIB) and global function (CIBIC+).
The study's two primary endpoints were the SIB and the CIBIC+. The change in total scores from baseline to week 24 on the SIB was 2.6 points in the Aricept 23 mg tablet group compared to 0.4 points in the Aricept 10 mg tablet group, resulting in a treatment difference that was statistically significant. This was based on the data from the intent-to-treat (ITT) population (ITT was 1,371 patients, p = 0.0001), with similar results for an analysis using data from the observed cases (1,084 patients who finished the study).
For the CIBIC+, the overall change score at week 24 was 4.23 in the Aricept 23 mg tablet group compared to 4.29 in the 10 mg tablet group (ITT, p = 0.1789), but this difference was not statistically significant.
In the pivotal trial, the most common adverse events (greater than or equal to 5 percent and greater than the 10 mg tablet group) with Aricept 23 mg tablet versus Aricept 10 mg tablet, respectively, were nausea (11.8 percent vs. 3.4 percent), vomiting (9.2 percent vs. 2.5 percent), diarrhea (8.3 percent vs. 5.3 percent), and anorexia (5.3 percent vs. 1.7 percent).