Galantamine (Razadyne) Lowers Mortality in Alzheimer’s Patients
Smaller cognitive decline also seen versus placebo (Dec. 5)
New study findings have shown a significantly lower mortality rate in patients with Alzheimer’s disease (AD) who were treated with galantamine (Razadyne, Janssen Pharmaceuticals) — approved for the treatment of mild to moderately severe AD — versus those who received placebo. Patients treated with galantamine also had a smaller decline in cognitive impairment after 2 years compared with patients in the placebo group, according to data presented at the American College of Neuropsychopharmacology 51st Annual Meeting in Hollywood, Fla. Janssen Research & Development sponsored the study.
At the trial’s final interim mortality analysis, an independent Data Safety Monitoring Board recommended early termination of the study due to an imbalance of deaths between the treatment group and the placebo group. Subsequent unblinding of the data indicated that the mortality rate was significantly lower in patients treated with galantamine compared with those who received placebo (3.1% vs. 4.9%, respectively; P = 0.021). In the final analysis, a total of 89 deaths were recorded: 33 (3.2%) in the galantamine group and 56 (5.5%) in the placebo group (P = 0.011).
The patients treated with galantamine also had significantly less cognitive decline — measured by the change from baseline in the Mini Mental Status Evaluation (MMSE) at month 24 — compared with the placebo group. The mean MMSE scores deteriorated from a baseline of 19 to 17.5 and 16.9 for the galantamine and placebo groups, respectively (P < 0.001).
In addition, there was significantly more decline from baseline in the MMSE at month 6 in the placebo group compared with the galantamine group (P < 0.001). The change in activities of daily living — as measured by the Disability Assessment in Dementia (DAD) scores from baseline to month 24 — was significantly worse in the placebo group than in the galantamine group (P = 0.002).
The trial enrolled a total of 2,051 patients (1,028 in the galantamine group and 1,023 in the placebo group). The patients’ mean age was 73 years (range: 45 to 92 years). Most of the patients (65%) were women. The galantamine group initially received 8 mg of drug daily, and the dose was increased to 16 to 24 mg daily during the first 12 weeks of the study. Thereafter, patients were maintained on 16 to 24 mg of galantamine daily.
Galantamine is an acetylcholinesterase inhibitor approved to treat the symptoms of mild to moderate AD, such as memory loss. There is no evidence that galantamine alters the course of the underlying process of dementia. While the precise mechanism of galantamine's action is unknown, it is believed to achieve its therapeutic effect by increasing the concentration of the neurotransmitter acetylcholine by inhibiting the enzyme cholinesterase, which breaks down acetylcholine.
Although the cause of cognitive impairment in AD is not fully understood, it has been reported that neurons that produce acetylcholine, a neurotransmitter, degenerate in the brains of patients with the disorder. The degree of this neuronal loss has been correlated with the degree of cognitive impairment and the density of amyloid plaques (a neuropathological hallmark of AD).
Source: Johnson & Johnson; December 5, 2012.