July 2, 2008 -- Many Alzheimer's researchers deny that the failure of a promising remedy for the degenerative disease requires a return to the drawing board, saying the setback is not a death knell for drugs designed to target a protein in the brain considered the trigger for the disease.
Still, doctors are disappointed that the treatment fell short of expectations -- especially when its makers spent $60 million on it during the past year alone.
On June 30, Myriad Genetics Inc. announced that its drug Flurizan didn't improve cognitive function or performance of daily activities for people who have Alzheimer's disease. A recent clinical trial tested the drug for 18 months in patients with a mild form of the condition.
"We are disappointed that Flurizan failed to achieve significance in this study, and we will now discontinue development of this compound," Myriad's CEO Peter Meldrum said in a statement.
Flurizan targeted one type of protein in the brain called beta amyloid. Researchers believe that the protein forms clumps that clog the connections between brain cells, which may contribute to the symptoms of Alzheimer's, which include progressive memory loss.
It was hoped that Flurizan would decrease the production of beta amyloid and slow the progression of the disease.
However, many scientists say they were not surprised by the findings. In fact, they say they even expected the outcome after seeing the underwhelming results of an earlier trial of the drug.
"The bottom line is that Flurizan was a nonstarter from the very beginning," says Rudy Tanzi, professor of neurology at Harvard Medical School in Boston. Tanzi is also the co-founder and shareholder of two companies that develop Alzheimer's treatments.
When results released in 2006 did not show an overall positive effect of Flurizan on brain function, Myriad researchers narrowed the patient population to target a small subgroup of people who benefited from the drug. They used this population -- patients who had mild Alzheimer's disease and took a high dose of the drug -- in the most recent trial.
But by that time, the earlier trial had already "cast considerable doubt on the potency of the drug in Alzheimer's disease," says Dr. Sid Gilman, director of the Michigan Alzheimer's Disease Research Center in Ann Arbor, Mich.
"I have been skeptical of this all along," Gilman added.
Where to Go From Here
Doctors say that this latest defeat in the fight against Alzheimer's gives no indication of the state of research relating to the disease.
"Flurizan was the first shot on goal, but it was a shot from the 50-yard-line by a fifth grader," Tanzi says. "This is by no means a failure of all drugs that target amyloid beta."
Dr. Ronald Petersen, director of the Alzheimer's Disease Treatment Center at the Mayo Clinic in Rochester, Minn., agrees and says, "There are many other alternatives in the pipeline that show promise."
Among these are drugs aimed at various targets, Gilman says, including the immune system, receptors for various chemicals that bathe brain cells, and other pathways for stopping the pesky proteins that researchers believe contribute to Alzheimer's symptoms.
But treating and curing the condition may require a tag team of therapies to achieve the most effective results.
"I suspect that the reality is that attacking the amyloid cascade is a complicated issue, and no single therapeutic strategy is likely to be the final answer," Petersen says.
Scientists are optimistic that even with Flurizan's demise, a plausible treatment will emerge soon.
"History has shown that when you have a new mechanism and a new target, inevitably the first wave of drugs is usually the worst," Tanzi says, referring to the findings from Flurizan. "In these situations you need to be patient and wait for the second or third wave of drugs. ... That wave is coming."