Health regulators are reviewing the safety of a drug for Alzheimer's disease after data from two clinical trials indicated that people taking it had a much higher death rate than those taking a placebo.
The review of the drug, Reminyl, was announced Friday by Johnson & Johnson, which said it was in discussions with the Food and Drug Administration and regulators in Europe and Canada.
The trials, which involved about 2,000 patients in 16 countries, were looking at whether Reminyl could be used to treat mild cognitive impairment, a form of memory loss that is often a precursor to Alzheimer's disease. Reminyl is approved in 69 countries as a treatment for mild to moderate Alzheimer's but not for mild cognitive impairment.
In the trials, which lasted two years, 15 patients taking Reminyl died compared with five taking the placebo. There were various causes of death but many were from heart attacks and strokes, a company spokeswoman, Carol Goodrich, said.
The announcement comes at a time of heightened concern over the safety of widely used drugs after the withdrawal from the market of Merck's pain reliever Vioxx, which studies indicated posed an increased risk of heart attacks and strokes.
Johnson & Johnson said that the overall number of deaths in the trials was low for the elderly population in the trial and that the incidence of serious side effects was the same for patients getting the drug and the placebo. Also, it said, the investigators in the trials had not thought the drug caused any of the deaths. The results were reported to regulatory authorities in August and presented at medical conferences, a company spokeswoman, Carol Goodrich said. Asked why an announcement was being made only now, Goodrich said regulators in Europe and Canada had met with the company this week to obtain more data and were preparing to post information about the trials on their Web sites.
She said the information would still support the use of the drug for Alzheimer's disease.
A spokeswoman for Health Canada, Carole Saindon, said data was being analyzed and conclusions would be posted when ready. "It's very important that patients don't stop taking the medication without consulting their doctor first," Saindon said. A spokeswoman for the FDA, Kathleen Quinn, said the agency was looking at the data. European regulators could not be reached.
Reminyl was also approved on the basis of six-month studies but the mild cognitive impairment trials lasted two years, increasing their chances of detecting side effects. Nevertheless, the Johnson & Johnson analysis said the excess of deaths in the mild cognitive impairment trials was evident by six months, while no such excess was seen in the Alzheimer's trials.
Reminyl was not effective in the trials at preventing progression to dementia, so the company is no longer pursuing that use, Goodrich said. No drugs have been approved for mild cognitive impairment.
Reminyl, known generically as galantamine, was co-developed with Shire Pharmaceuticals of Britain. Sales for Johnson & Johnson are estimated at about US$200 million a year. The drug, extracted from daffodil bulbs, is a cholinesterase inhibitor, which works by increasing the levels of acetylcholine, a chemical that transmits nerve signals in the brain. Others in this class include Aricept, sold by Pfizer and Eisai, and Exelon from Novartis. Public Citizen, the watchdog group, recommends against using Reminyl or the other drugs in its class, saying they have minimal benefit and the effectiveness and safety of taking them longer than six months is not known, said Sidney Wolfe, director of health research.