Regulatory authorities are reviewing data suggesting that galantamine (Reminyl), a cholinesterase inhibitor licensed for mild to moderate dementia in Alzheimer's disease, was associated with increased mortality among patients with mild cognitive impairment.
The manufacturer, Johnson & Johnson Pharmaceutical Research & Development, made the announcement last week, following two trials that it conducted. The studies combined included 2048 people aged 50 years and over with mild cognitive impairment (insufficient impairment to be diagnosed as dementia). The participants were randomly assigned to receive 8 mg or 12 mg twice daily galantamine or placebo for 24 months to see if the drug slowed progression to dementia.
Initial results showed more deaths in those treated with the drug (13/1026) than with placebo (2/1022) (hazard ratio for death 4.86 (95% confidence interval 1.76 to 13.40) during the double blind phase of the studies. Causes of death in patients taking galantamine included sudden death, heart attack, and suicide.
Preliminary evidence showed that some participants may have discontinued the study and then died. The manufacturer therefore looked in more detail at deaths among 1800 of the participants, 895 of whom were given placebo and 905 of whom were given galantamine. Twenty people (15 who were taking galantamine and five taking placebo) died from various causes during the double blind phase of the studies (relative risk of death for patients taking galantamine 3.04 (1.26 to 7.32)).
A report posted on the Pharmaceutical Research and Manufacturers of America clinical trials website (www.clinicalstudyresults.org) last week said the difference in death rates between the placebo and drug groups became apparent within the first three months of treatment whereas in placebo controlled studies of up to six months among patients with dementia death rates did not differ between galantamine and placebo.
The report concluded that the findings suggested that mortality from the mild cognitive impairment studies could not be generalised to the previous research on Alzheimer's disease, Alzheimer's disease with cerebrovascular disease, and vascular dementia.
Johnson & Johnson said in a statement that it was analysing the additional results and was discussing them with regulatory authorities, including the US Food and Drug Administration and the European Medicines Agency. "Mortality rates were low in both the galantamine and placebo groups in this two year study compared to expected rates in this population or in patients with Alzheimer's disease," it added.
A company spokesperson said that the deaths were mostly cerebrovascular or cardiovascular. The company had no plans to do further research on galantamine in the treatment of mild cognitive impairment, she said. The requirement to monitor patients treated with the drug had not changed, she added.