NEW YORK Experimental Alzheimer's drugs from Roche Holding AG and Eli Lilly & Co have been selected for a high-profile clinical trial to test whether it is possible to prevent the brain-wasting disease from developing in at-risk patients.
The trial, expected to start early next year, will enroll 160 patients worldwide with inherited gene mutations that typically lead to Alzheimer's symptoms when they are as young as in their 30s, Washington University in St. Louis said on Wednesday in announcing the drugs' selection.
Drug studies over the past decade have tried and failed to slow progression of Alzheimer's among patients who already have dementia. The hope is that success in arresting symptoms in patients who are so highly predisposed to develop the disease will show the way to preventing Alzheimer's in a much wider population.
"We're going in with three different drugs, with three different mechanisms of action, to find out which works best," said Dr. Randall Bateman, a neurologist at the Washington University School of Medicine who will lead the trial.
Bateman, in a telephone interview, said about half the patients in the trial will have no symptoms at all when the study begins, while the rest will have very mild symptoms.
Dr. James Galvin, a neurologist at New York University Langone Medical Center, said such a prevention trial involving people at high genetic risk of Alzheimer's disease would require relatively few patients and could produce results within a few years.
"Each family has a genetic mutation with a defined age of onset of disease, so you can start giving the drug a certain number of years before the predicted onset," Gavin said. "If they don't get the diseease by then, you've prevented it or delayed it."
By contrast, he said a prevention trial in the general population might need to last 20 years or longer "because you wouldn't know who will get the disease or be able to predict when."
As many as 5 million people in the United States and 36 million globally are believed to have Alzheimer's, the most common form of dementia. The U.S. figure for people 65 or older may triple by 2050 as the population ages, according to the Alzheimer's Association.
The drugs chosen for the study are Roche's gantenerumab and Lilly's solanezumab. Also under consideration is a second experimental Lilly drug called a beta-secretase inhibitor, designed to reduce the beta amyloid proteins produced by the body and slow the accumulation of toxic brain plaques linked to Alzheimer's.
An experimental treatment from Pfizer Inc and Johnson & Johnson, called bapineuzumab, did not make the cut after data from two large trials presented over the summer showed it failed to help patients with mild to moderate symptoms.
MILD HOPE FOR LILLY DRUG
Researchers in August said Lilly's solanezumab also failed to prevent decline in cognitive and physical function among patients with mild to moderate Alzheimer's in two large late-stage studies. The drug, a monoclonal antibody similar to bapineuzumab, attacks beta amyloid.
But hopes for solanezumab were revived on Monday when Lilly said an analysis of pooled data from the two studies showed solanezumab led to a 34 percent reduction in memory decline for patients with mild symptoms over a period of 18 months. It said the change was statistically significant.
Wall Street analysts expect Lilly will seek marketing approval from the drug, but will likely need to first complete a large costly new trial among patients with mild symptoms to win over health regulators.
Roche began a late-stage study of gantenerumab in late 2010 for patients who have yet to develop dementia, and expects results in 2015. The Swiss drugmaker has high hopes for the drug because previous brain scan tests have shown it can reduce amyloid plaques in the brain.
Shares of Lilly, which had gained more than 7 percent since its latest solanezumab data were unveiled on Monday, fell 3 percent to close at $50.23 on Wednesday. Shares of Roche fell 1.2 percent amid a 0.8 percent decline in the ARCA Pharmaceutical Index of large U.S. and European drugmakers.
The new prevention trial will be led by the Dominantly Inherited Alzheimer's Network Trials Unit (DIAN TU) at Washington University in St Louis. The unit's work is supported by the DIAN, a federally funded collaboration of Alzheimer's research centers, the Alzheimer's Association and a consortium of 10 drugmakers.