No Benefit for Dimebon in Huntington’s
An antihistamine that failed to work in Alzheimer’s disease also fell short of expectations in Huntington’s disease, researchers reported.
In a randomized controlled trial, latrepirdine (Dimebon) didn’t improve cognition or global function compared with placebo, Ray Dorsey, MD, of Johns Hopkins, and colleagues reported online in the Archives of Neurology.
Currently, medications can mitigate the symptoms of movement problems that accompany Huntington’s, but there is no treatment for its cognitive dysfunction.
Though it was initially developed as an antihistamine, latrepirdine was shown in some studies to aid mitochondrial function, which might be impaired in Huntington disease.
Researchers had also speculated that the drug would alleviate the symptoms of Alzheimer’s disease, but it flopped in a major trial.
Dorsey and colleagues conducted a randomized, controlled, double-blind trial at 64 centers in Australia, Europe, and North America in 403 patients with mild to moderate Huntington’s and baseline cognitive impairment.
Patients were given placebo or 20 mg latrepirdine 3 times a day for 26 weeks. Primary endpoints were improvements in cognition and global function, as measured by the Mini-Mental State Exam score and the Clinician Interview-Based Impression of Change, respectively.
Overall, the researchers found no differences in improvements in cognition between the drug and placebo groups (1.5-point improvement versus 1.3 point improvement, P=0.39).
Likewise there were no differences in global function between groups as measured by both clinician and caregiver interview (P=0.84).
And there were no significant effects on any of the secondary outcome measures including behavior, motor function, or activities of daily living, they added.
Adverse events were similar between groups (68.5% and 68%), and the most common complications were falls, worsening chorea, and somnolence.
Only fatigue and dry mouth occurred more frequently in the latrepirdine group, the researchers wrote.
They also cautioned that there was more weight gain among patients who took the drug (0.97 kg [2.14 lbs] versus 0.04 kg [0.09 lbs], P=0.01).
There are a number of reasons why the drug may not have worked in these patients, the researchers said. The failure could be due to inadequate dosing, insufficient duration of treatment, inappropriate outcome measures, or lack of therapeutic benefit in this population.
And since even the patients on placebo saw cognitive improvements, it raises questions about the effects of placebo in other Huntington’s trials, they noted.
“Although the results of this study were disappointing, the trial lays the foundation for future investigations of Huntington’s disease experimental therapeutics aimed at cognition,” Dorsey and colleagues concluded, adding that the trial was the largest “by far” of any drug aimed specifically at improving cognition in the disease.
The study was supported by grants from Medivation and Pfizer.
The researchers reported relationships with Medivation, Pfizer, Elan, SIENA, Teva, Boehringer Ingelheim, Impax, UCB, GE Healthcare, IPSEN, Novartis, Solvay, Quintiles, Biogen Idec, Allergan, GlaxoSmithKline, Bial, Lundbeck, Chelsea Therapeutics, Impax, Santhera, Merck Serono, Synosis, Schering Plough, Shire, XenoPort, Addex, Adamas, Noven, PICO-Tesla, Schwartz, Genzyme, Acadia, Molecular Biometrics, Abbott, Acorda, Aptiv, Biotie, Bioaail, Ceregene, Civitas, Clintrex, Cynapsus, Isis, Knopp, Eli Lilly, Link Medicine, LZ THerapeutics, Merz, Orion, Otsuka, Pharm2B, Phytopharm, Siena, Synagile, Vaccinex, Vectura, NeuroSearch, AOP Orphan, Medesia, Amarin, and Temmler.
Primary source: Archives of Neurology
Source reference: Dorsey ER, et al “A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease” Arch Neurol 2012; DOI: 10.1001/2013.jamaneurol.382.