Data highlight overall patient benefits of Reminyl™ (galantamine) treatment over 1 year
June 27, 2000 -- Two new Phase III studies published today for the first time in Neurology* show that a new treatment for Alzheimer's disease with dual mechanism of action -- Reminyl™ (galantamine) -- significantly improves cognition, global function and behavioural symptoms of Alzheimer's disease over a period of 1 year.
The two studies, conducted in the US, form part of the pivotal trials programme for galantamine which are now being reviewed by regulatory authorities worldwide. Reminyl was recently approved for the treatment of mild to moderate Alzheimer's disease in Sweden and Switzerland.
"There are at least two victims in this illness: the patient and the caregiver," says lead author Pierre Tariot, MD, professor of psychiatry, medicine and neurology at the University of Rochester Medical Center in New York. "Maintaining the patient's ability to remember, and to think clearly and rationally, is still a major treatment goal. But just as important is a patient's ability to perform simple tasks such as bathing, dressing and eating, and to interact with others. Anything that improves or helps stabilize this ability to function helps ease the burden on caregivers. We need more treatment options to help patients and caregivers achieve these goals, and this study suggests that galantamine offers potential benefits."
12 month study
The first study showed that patients with mild to moderate Alzheimer's disease treated with 24mg/day galantamine continuously for 12 months were maintained at or above baseline as measured on the ADAS-Cog, and were also able to maintain activities of daily functioning for one year. A total of 636 patients were randomized to receive galantamine of 24 or 32 mg/day or placebo for the first six months. Following the conclusion of the double-blind period, an open-label extension ran for six months and involved 353 patients who were treated with galantamine 24mg/day.
Analysis showed that galantamine treatment significantly improved cognitive function relative to placebo: the treatment effects were 3.9 points (24mg/day) and 3.8 points (32.mg/day) on the ADAS-Cog at month six (p<0.001). Both doses produced a better outcome on CIBIC-Plus** than placebo (p<0.05). Benefits on cognitive and daily functioning were maintained for 12 months with galantamine 24mg/day, the maximum recommended daily maintenance dose.
5 Month Study
A further multi-centre, double-blind, placebo-controlled study involving 978 patients with mild to moderate Alzheimer's disease was designed to investigate the efficacy and tolerability of galantamine over a 5 month period. Patients treated with 16 and 24mg daily doses of galantamine scored higher on efficacy measures than placebo groups. Cognitive scores for 16 and 24mg groups were also significantly improved at the 5 month endpoint in comparison to a recorded deterioration in the placebo group (p<0.001). In addition, using the CIBIC-Plus scale, physicians judged patients' overall ability to function as improved or remaining stable in 64 and 68 percent of patients who took 16 or 24mg of Reminyl respectively, compared to 47% of those who received placebo (p<0.001)
During the 5 month-study, the patients who received16 or 24mg of Reminyl had a significantly smaller decrease in ADL scores than patients on placebo (p<0.01). Behavioural symptoms also stabilised during the trial: patients treated with either 16mg/day or 24mg/day of Reminyl did not deteriorate compared to placebo.
Patients were randomized to receive different treatments. The ADAS-Cog, CIBIC-Plus, Alzheimer's Disease Cooperative Study Inventory and Neuropsychiatric Inventory (NPI) scales were used to measure the results.
Throughout the course of the study, the proportion of patients reporting any serious adverse effects was similar for both patients taking 16 mg. of galantamine and those receiving placebo (10% vs. 11% respectively).
Novel Dual Mode of Action
Research indicates that galantamine, unlike other Alzheimer's treatments currently available, has a dual mechanism of action. Decreased levels of acetylcholine, caused by the death of acetylcholine neurones are known to be related to the symptoms of Alzheimer's disease. In addition to preserving levels of acetylcholine in the brain by blocking the action of the enzyme acetylcholinesterase (which inactivates acetylcholine), laboratory research has shown that galantamine also appears to act on the brain's nicotinic receptors. The "modulation" of these receptors could lead to release of more acetylcholine. 1,2,3 The clinical significance of this finding is not yet known, but is being investigated further by Janssen.
For further information please contact:
Melissa Katz, International Public Affairs 32-1460-5910
Janssen Pharmaceutica
Roseann Ward 44-207-465-8752
Ketchum
roseann.ward@ketchumcomms.co.uk
John Gisborne 44-207-465-8753
Ketchum
John.gisborne@ketchumcomms.co.uk
References:
1. Schrattenholz A et al. Agonist Responses of Neuronal Nicotinic Acetylcholine Receptors are Potentiated by a Novel Class of Allosterically Acting Ligands. Molecular Pharmacology. 1996; 49:1-6
2. Maelicke A. Nicotinic Receptors in the Central Nervous System. 6th International Conference on Alzheimer's Disease and Related Disorders. July 18, 1998; Amsterdam, The Netherlands
3. Vidal, C. Nicotinic Receptors in the Brain: Molecular Biology, Function, and Therapeutics. Molecular and Chemical Neuropathology. 1996;28:3-11
*The ADAS-Cog (Alzheimer's Disease Assessment Scale, cognitive portion) is a scale which measures cognitive performance, the ability to learn, remember and make decisions. It is a 70-point scale where 0 = no impairment and 70 = severe impairment.
**The CIBIC-Plus (Clinicians Interview Based Impression of Change with Caregiver Input) is a standard scale used to assess cognition, functioning and behaviour. "Plus" indicates the inclusion of information from caregivers about activities of daily living.
Reminyl™ (galantamine) is being developed by the Janssen Research Foundation, under a co-development agreement with UK-based Shire Pharmaceuticals Group plc. It was recently approved in Sweden, and is currently being considered by other countries as part of the European Union Mutual Recognition Procedure. A new drug application (NDA) was filed with the U.S. FDA in September 1999. If approved by the respective regulatory agencies, galantamine will be marketed under the trade name Reminyl™ by Janssen Pharmaceutica in the United States, by Janssen-Ortho in Canada and by Janssen-Cilag elsewhere -- with the exception of the United Kingdom and Ireland, where it will be sold by Shire under a co-promotion agreement with Janssen-Cilag.
Janssen Research Foundation, an affiliate of Janssen Pharmaceutica, is headquartered in Beerse, Belgium. Janssen-Cilag has operating companies in 32 countries, including the United States. A wholly owned subsidiary of Johnson & Johnson, it is a leader in central nervous system research. Other areas of research include anaesthesia, oncology and gastroenterology.
Shire Pharmaceuticals Group plc is an emerging pharmaceutical company focused primarily on two therapeutic areas: central nervous system disorders and metabolic bone disease, with sales, marketing and R&D operations in the UK and United States.
Journal
Neurology