Disappointing results have been reported from the first study in the ongoing phase 3 program evaluating the efficacy of the investigational drug idalopirdine (Lundbeck/Otsuka) for the symptomatic treatment of patients with mild-to-moderate Alzheimer’s disease (AD).
In the STARSHINE trial, idalopirdine showed a weak efficacy profile, as neither of the two dosages used in the study met the primary endpoint of a reduction in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-cog) total score when added to donepezil. In addition, the secondary endpoints failed to show separation from placebo.
The two remaining studies in the phase 3 program (STARBEAM and STARBRIGHT) will continue as planned, and data are expected in the first quarter of 2017.
Idalopirdine is a selective 5-HT6 receptor antagonist. The 5-HT6 receptor is expressed in brain regions involved in cognition, such as the cortex and the hippocampus, and modulates the activity of multiple neurotransmitter systems.
Through 5-HT6 receptors expressed on glutamatergic neurons and GABAergic interneurons, idalopirdine is believed to modulate the balance between excitation (glutamate) and inhibition (GABA) in the brain. When administered with donepezil, idalopirdine potentiates the effects of acetylcholinesterase inhibitors (AChEIs) on acetycholine levels and on neuronal activity in the cortex and hippocampus.
Positive results from a 24-week phase 2 study of idalopirdine as adjunctive therapy in patients with moderate AD have been presented. To confirm these findings, a large phase 3 program evaluating idalopirdine as an adjunct to AChEIs in patients with mild-to-moderate AD is ongoing. The development program is part of an alliance between Lundbeck and Otsuka Pharmaceuticals Co. Ltd.
Source: Lundbeck; September 22, 2016.