UPDATE 3-Roche, Lilly drugs set for Alzheimer's prevention trial

* Trial to start in early 2013, enroll 160 patients

* Focus on patients with gene mutations that put them atrisk early

* Will test new theory on preventing Alzheimer's

(Adds comment from lead researcher, neurologist; updates stockprice)

By Ransdell Pierson

NEW YORK, Oct 10 (Reuters) - Experimental Alzheimer's drugsfrom Roche Holding AG and Eli Lilly & Co havebeen selected for a high-profile clinical trial to test whetherit is possible to prevent the brain-wasting disease fromdeveloping in at-risk patients.

The trial, expected to start early next year, will enroll160 patients worldwide with inherited gene mutations thattypically lead to Alzheimer's symptoms when they are as young asin their 30s, Washington University in St. Louis said onWednesday in announcing the drugs' selection.

Drug studies over the past decade have tried and failed toslow progression of Alzheimer's among patients who already havedementia. The hope is that success in arresting symptoms inpatients who are so highly predisposed to develop the diseasewill show the way to preventing Alzheimer's in a much widerpopulation.

"We're going in with three different drugs, with threedifferent mechanisms of action, to find out which works best,"said Dr. Randall Bateman, a neurologist at the WashingtonUniversity School of Medicine who will lead the trial.

Bateman, in a telephone interview, said about half thepatients in the trial will have no symptoms at all when thestudy begins, while the rest will have very mild symptoms.

Dr. James Galvin, a neurologist at New York UniversityLangone Medical Center, said such a prevention trial involvingpeople at high genetic risk of Alzheimer's disease would requirerelatively few patients and could produce results within a fewyears.

"Each family has a genetic mutation with a defined age ofonset of disease, so you can start giving the drug a certainnumber of years before the predicted onset," Gavin said. "Ifthey don't get the diseease by then, you've prevented it ordelayed it."

By contrast, he said a prevention trial in the generalpopulation might need to last 20 years or longer "because youwouldn't know who will get the disease or be able to predictwhen."

As many as 5 million people in the United States and 36million globally are believed to have Alzheimer's, the mostcommon form of dementia. The U.S. figure for people 65 or oldermay triple by 2050 as the population ages, according to theAlzheimer's Association.

The drugs chosen for the study are Roche's gantenerumab andLilly's solanezumab. Also under consideration is a secondexperimental Lilly drug called a beta-secretase inhibitor,designed to reduce the beta amyloid proteins produced by thebody and slow the accumulation of toxic brain plaques linked toAlzheimer's.

An experimental treatment from Pfizer Inc andJohnson & Johnson , called bapineuzumab, did not make thecut after data from two large trials presented over the summershowed it failed to help patients with mild to moderatesymptoms.


Researchers in August said Lilly's solanezumab also failedto prevent decline in cognitive and physical function amongpatients with mild to moderate Alzheimer's in two largelate-stage studies. The drug, a monoclonal antibody similar tobapineuzumab, attacks beta amyloid.

But hopes for solanezumab were revived on Monday when Lillysaid an analysis of pooled data from the two studies showedsolanezumab led to a 34 percent reduction in memory decline forpatients with mild symptoms over a period of 18 months. It saidthe change was statistically significant.

Wall Street analysts expect Lilly will seek marketingapproval from the drug, but will likely need to first complete alarge costly new trial among patients with mild symptoms to winover health regulators.

Roche began a late-stage study of gantenerumab in late 2010for patients who have yet to develop dementia, and expectsresults in 2015. The Swiss drugmaker has high hopes for the drugbecause previous brain scan tests have shown it can reduceamyloid plaques in the brain.

Shares of Lilly, which had gained more than 7 percent sinceits latest solanezumab data were unveiled on Monday, fell 3percent to close at $50.23 on Wednesday. Shares of Roche fell1.2 percent amid a 0.8 percent decline in the ARCAPharmaceutical Index of large U.S. and Europeandrugmakers.

The new prevention trial will be led by the DominantlyInherited Alzheimer's Network Trials Unit (DIAN TU) atWashington University in St Louis. The unit's work is supportedby the DIAN, a federally funded collaboration of Alzheimer'sresearch centers, the Alzheimer's Association and a consortiumof 10 drugmakers.

(Reporting By Ransdell Pierson; Editing by Michele Gershberg,John Wallace, David Gregorio and Richard Chang)

((ransdell.pierson@thomsonreuters.com)(646 223 6030))