The Health Sciences Authority (HSA) has just received a safety alert from Johnson & Johnson's Pharmaceutical Research Division that its company has terminated, worldwide, its Reminyl® (galantamine) trials conducted for an exploratory indication, i.e. mild cognitive impairment (MCI). This is due to concern over the increase in the mortality rate in the treatment group compared to the placebo group. Singapore did not participate in the trials for MCI.

Reminyl® (galantamine) is a selective acetylcholinesterase inhibitor and is approved locally for the treatment of mild to moderately severe dementia of the Alzheimer type.

Results from 2 new, unpublished, scientific studies investigating patients with MCI showed an increased mortality in the group receiving galantamine as compared to the group receiving placebo. The purpose of the new studies was to see if the onset of dementia could be delayed in patients with MCI, but the effect was no different from that seen in the placebo group.

Initial analysis of the two studies comparing galantamine and placebo in MCI patients showed that a total of 15 patients died during treatment with galantamine, while there were 5 deaths in those receiving placebo. The relative risk was 3.04 (1.27-7.32; 95% CI) and the excess risk was 1% (0.4-2.4; 95% CI). This analysis is preliminary in nature, as it has not been possible yet to follow up all included patients. The cause of death in each case varied, but was mainly of a cardiovascular or cerebrovascular nature, with the median age at death being 79 years (range 58-93). In total, about 1,000 patients had received galantamine and about 1,000 patients had been on placebo for 2 years. The studies were performed in several European countries, Australia, Argentina and in the US.

These are the first studies of galantamine with a treatment duration of two years. The majority of previous studies investigated the treatment of Alzheimer's dementia for a period of up to 6 months based on internationally accepted criteria. In these earlier studies, no increased mortality was found in comparison to placebo.

HSA has requested for more information on the unpublished data and will also be closely monitoring the actions taken by other regulatory agencies. We will keep our healthcare professionals updated as more information becomes available.

Pending further analysis of the trial data, treatment using Reminyl® outside of its approved indication is not advised.