30 Sep 2016

Topline data from one of three ongoing Phase 3 trials for idalopirdine indicate that patients with mild to moderate Alzheimer’s disease who took the drug declined just as fast as did those on placebo. According to a press release, drug sponsor H. Lundbeck A/S, Valby, Denmark, plans to finish the other two trials and an open-label extension as scheduled.

Exactly how idalopirdine might prevent cognitive decline is unclear, but some studies suggest it boosts cholinergic, glutamatergic, noradrenergic, and dopaminergic neurotransmission. Also called Lu AE58054, the compound blocks 5-HT6 serotonin receptors and stimulates the release of acetylcholine, suggesting it might enhance the effects of acetylcholinesterase inhibitors (Ramírez 2013; Galimberti and Scarpini, 2015). In combination with donepezil, one of three cholinesterase inhibitors approved for treating AD, idalopirdine raised acetylcholine levels in the hippocampi of rats (Herrik et al. 2016). A Phase 2 trial in patients with moderate AD suggested that idalopirdine and donepezil together slowed decline more effectively than the cholinesterase inhibitor by itself (Oct 2014 news; Jun 2012 news). 

In the six-month Phase 3 trial dubbed STARSHINE, 932 patients with mild to moderate AD received either 30 or 60 mg of idalopirdine or placebo daily, in addition to 10 mg of donepezil. While the company says their drug was safe and well-tolerated, neither dose improved performance on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) beyond what was seen with donepezil alone. Idalopirdine also failed to improve secondary outcomes, which included activities of daily living, neuropsychiatric symptoms, and cognition measured by the mini-mental state examination (MMSE).

Two other six-month Phase 3 trials are ongoing. STARBEAM tests lower doses of the compound, while STARBRIGHT combines it with other acetylcholinesterase inhibitors. An open-label extension trial, will examine long-term safety and tolerability over seven additional months in patients enrolled in STARBEAM and STARSHINE.—Gwyneth Dickey Zakaib