May 8, 2017

Otsuka Pharmaceutical and H. Lundbeck reported results of two phase III clinical trials of brexpiprazole in the treatment of agitation in patients with dementia related to Alzheimer’s disease. Both trials were randomized, double-blind, placebo-controlled studies that enrolled a combined total of approximately 700 participants. Trial participants were between 51 and 90 years of age with a diagnosis of probable Alzheimer’s disease and symptoms of agitation. These studies were conducted in multiple countries in North America and Europe, and in the Russian Federation. One of the trials studied fixed doses of either 1 or 2mg per day of brexpiprazole or placebo, while the other trial studied a flexible-dose range of 0.5mg, 1mg or 2mg per day of brexpiprazole, or placebo. Both trials were 12 weeks in duration. In the first study, the improvement in the primary endpoint of Cohen-Mansfield Agitation Inventory (CMAI) for 2mg brexpiprazole was statistically better than placebo (p<0.05) and appeared more robust than the improvements on the key secondary endpoint of Clinical Global Impression-Severity of Illness (CGI-S) (p>0.05). In the second study, the improvements in the primary endpoint of CMAI (p>0.05) appeared less robust than improvements observed on the key secondary endpoint of CGI-S (p<0.05). In both studies, there was variability in the data from different countries, perhaps associated with differing standards of care; the data from Russian sites showed especially poor separation between placebo and drug. Regarding safety and tolerability, both studies confirmed the profile of brexpiprazole as observed in the clinical trials for schizophrenia and for adjunctive treatment of major depressive disorder (MDD). The most common adverse events in patients receiving brexpiprazole versus placebo (incidence >3% and greater than placebo) were insomnia (4.7% vs. 3.3%), agitation (3.5% vs. 2.9%) and somnolence (3.3% vs. 2.2%). Overall mortality during the studies was 0.86% and none of the deaths were considered to be related to treatment. The companies plan to meet with the FDA to discuss the results of the studies.

March 6, 2006

Allon Therapeutics has issued positive results of a phase I trial of AL-208, for the treatment of mild cognitive impairment (MCI) following coronary artery bypass graft surgery (CABG). Trial data yielded a positive overall safety profile, with no serious adverse events reported and good tolerability. This open-label single-ascending-dose study enrolled 64 healthy volunteers in San Antonio, who received one of 6 doses of the drug (10 mcg, 30 mcg, 50 mcg, 100 mcg, 200 mcg or 300 mcg). Based on these results, the company announced plans to initiate both a phase IIa efficacy trial in post-CABG MCI and a phase Ib safety, tolerability and pharmacokinetic trial for the treatment of chronic neurodegenerative conditions.

D-Pharm reported positive results of a phase II trial of DP-VPA, for the treatment of epilepsy, in the journal Drugs of the Future. Results yielded a significant reduction in mean (30%) and median (23%) seizure frequency, relative to placebo (p=0.02). In addition, carryover-efficacy was noted in reducing seizure frequency after the treatment period. No serious treatment related adverse events were reported. This double-blind, placebo-controlled cross-over study treated epileptic patients with DP-VPA or placebo for 28 days, in addition to background treatment.

May 16, 2005

Inflazyme and Helicon announced positive results of a series of phase I trials of their phosphodiesterase-4 (PDE4) inhibitor IPL455,903, for the treatment of cognitive impairment. Data from the studies yielded a positive safety profile, with no serious adverse events reported and no incidence of emesis, a common tolerability concern with PDE4 inhibitors. Pharmacokinetic analysis indicated a clinically useful plasma profile, with drug absorption not strongly influenced by food intake. All the trials in the series were open-label ascending-dose studies, which enrolled a combined 50 healthy adult volunteers. Subjects received a single-dose (5 mg-405 mg) of the drug or placebo orally, and were monitored for safety, tolerability and pharmacokinetics. Based on these results, the companies announced plans for 2-week multiple- ascending dose phase I studies in healthy volunteers, to be followed by phase IIa safety and efficacy studies in subjects with learning and memory disorders.

February 4, 2002

Study results indicate that treatment with Aricept (donepezil hydrochloride) significantly improves the cognitive and global function of vascular dementia (VaD) subjects compared to placebo. The double-blind, randomized, placebo-controlled trial included subjects with VaD and excluded those with a diagnosis of Alzheimer's disease. Subjects treated with Aricept (5 mg or 10 mg) showed significant improvement in their cognitive function compared to placebo-treated subjects as measured by the Alzheimer's Disease Assessment Scale (ADAS-cog). Aricept also produced significant improvements in global function compared to placebo, as measured by the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC-plus). Aricept is being developed according to a partnership between Pfizer and Eisai.