June 10, 2008
Patients with mild Alzheimer's disease who took the experimental drug Flurizan showed less decline in their ability to carry out everyday tasks than those taking a dummy pill, a mid-stage British study found. The drug, known generically as tarenflurbil, has shown promise in early trials for treating memory loss and other symptoms of Alzheimer's. More testing in larger numbers of people has been carried out, and the results of these larger trials will be made available this summer.
The findings are important because Flurizan is one of a group a new drugs that inhibits the buildup of toxic form of beta-amyloid, a protein that builds up in the brains of those with Alzheimer's disease. Many researchers believe that drugs that act on beta-amyloid may attack Alzheimer's at its core, thereby stemming the relentless downward spiral that occurs in the disease.
Currently available drugs for Alzheimer's, like Aricept, Razadyne, Exelon, and Namenda, may ease symptoms for a time in some patients. But these drugs do not slow the long-term progression of Alzheimer's.
Researchers hope that disease-modifying drugs that inhibit beta-amyloid may halt, or even reverse, the progressive memory loss and thought problems that devastate those with Alzheimer's disease. Flurizan acts on an enzyme called gamma-secretase, which cleaves beta-amyloid into a toxic form that builds up in the brain.
Although these results are promising, the results of a recently completed, large clinical trial will help tell whether Flurizan provides real benefit in people living with dementia.
Other promising drugs that act on beta-amyloid are also undergoing testing. It may take years, however, before most are proven safe and effective against Alzheimer's disease.
What the Study Showed
In the current study, researchers at Oxford University in the United Kingdom studied 210 men and women in the early stages of Alzheimer's. Some of the patients got 800 milligrams of Flurizan twice a day, while others got half that dose. A third group took a look-alike placebo pill.
The study participants were given the drugs for a year. Then, for a second year, some in the placebo group were given Flurizan at either a 400 milligram or 800 milligram twice-daily dose.
The researchers found that individuals with mild Alzheimer's taking the highest dosage of the drug -- 800 milligrams twice a day for 24 months - had the lowest rates of functional decline. The findings support earlier research in mice that were specially bred to develop a disease similar to Alzheimer's in people. Those studies suggested that the drug provided benefits for learning and memory, especially when given early in the course of the disease.
Flurizan is derived from a class of drugs known as nonsteroidal anti-inflammatory agents, or Nsaids. But Flurizan itself is not an anti-inflammatory drug, or Nsaid, and therefore does not carry the common side effects like gastrointestinal distress of Nsaids. In mice, certain Nsaids help to prevent the toxic buildup of beta-amyloid in the brain. Others do not, and even a few Nsaids increase the production of toxic beta-amyloid.
The researchers concluded that "800 mg tarenflurbil twice per day was well-tolerated for up to 24 months of treatment, with evidence of a dose-related effect on measures of daily activities and global function in patients with mild AD ... these findings justify phase III studies of tarenfurbil at the 800 mg twice daily dose in patients with mild Alzheimer's disease."
The study was published online in The Lancet Neurology.
In an accompanying commentary, Dr. Paul Aisen of the University of California, San Diego, wrote: "With the need so enormous, and the potential effect of the benefit suggested by these phase II results, the effort is indeed justified despite the substantial uncertainty. In a few months, we will learn whether tarenflurbil will be the first anti-amyloid intervention to be efficacious in a pivotal trial."
Gordon K. Wilcock, Sandra E. Black, Suzanne B. Hendrix, et al: "Efficacy and Safety of Tarenflurbil in Mild to Moderate Alzheimer's Disease: A Randomised Phase II Trial." Lancet Neurology: Published online, April 30, 2008
Paul Aisen: "Tarenflurbil: A Shot on Goal." Lancet Neurology: Published online, April 30, 2008