Lilly Plans Big Alzheimer's Disease Study After Prior Failures

Drug & Device Development

Last Updated: 2013-07-12 10:20:25 -0400 (Reuters Health)

(Reuters) - Eli Lilly and Co plans this year to begin a new late-stage trial of solanezumab, its experimental treatment for Alzheimer's disease that failed in earlier testing to significantly slow progression of the degenerative neurological disease, the U.S. drugmaker said on Friday.

A pair of unsuccessful earlier Phase III studies last summer had involved patients with mild to moderate symptoms. But combined data from them showed the drug slowed cognitive decline by 34% in patients who started out with only mild symptoms, but without slowing declines in their ability to perform everyday tasks.

Lilly said the new Phase III trial, consequently, would only include patients with mild symptoms of Alzheimer's. It will consist of 2,100 people, considerably more than the total of about 1,300 with mild Alzheimer's in the earlier two Phase III studies.

The Indianapolis company plans to begin enrolling patients in the new study, called Expedition 3, before the end of September, and noted that patients would be treated for 18 months. But Lilly declined to speculate when it will have final data from the high-profile study.

Anthony Ware, Lilly's senior vice president for product development, expressed confidence that solanezumab would meet its main goals this time around, with a less-advanced patient population.

"We found results in Expedition 1 and Expedition 2 highly encouraging, and are planning for a success in this program," he said in an interview.

Solanezumab, which patients take by infusion, works by blocking the beta-amyloid protein that forms plaques in the brain that are believed to be a cause of the disease. Bapineuzumab, a similar drug being developed by Pfizer Inc, failed its main trial goals last year and has been largely written off.

An estimated 5 million Americans have Alzheimer's, the biggest cause of dementia. More than 35 million people worldwide are believed to have dementia, including Alzheimer's disease, and those numbers are expected to rise as more people live longer.

WRONG PATIENTS SCREENED

Eric Siemers, senior medical director of Lilly's Alzheimer's program, said an estimated 25% of patients in the two earlier Expedition trials might not actually have had beta-amyloid deposits or Alzheimer's disease, so solanezumab could not have helped them.

He said many patients were enrolled in those trials on the basis of symptoms, without undergoing sophisticated diagnostic procedures now available to confirm the presence of beta-amyloid deposits.

In the new study, Lilly's recently approved radioactive imaging agent, called Amyvid, will be used to screen patients, Siemers said. Biochemical measures in the spinal fluid can also help assess whether patients have Alzheimer's, he said.

Two independent studies of solanezumab, just getting off the ground, could also shed light on the drug's potential.

A study sponsored by the U.S. government will examine whether Alzheimer's can be slowed or prevented in older patients who have not yet developed significant memory problems.

The "A4" prevention study, set to begin by early next year, will select about 1,000 participants aged 70 to 85 who have varying levels of amyloid protein in their brains but no symptoms yet of Alzheimer's. Brigham and Women's Hospital, an affiliate of Harvard Medical School, is helping coordinate the three-year study, which may cost up to $100 million.

The researchers, who will select the patients by using Amyvid, are hoping solanezumab will reduce memory decline by perhaps 30%. But data from the "A4" study is not expected until 2018.

Solanezumab and an anti-amyloid drug being developed by Roche Holding AG were selected in October for another high-profile prevention trial, but it involves younger patients with a genetic high risk of developing Alzheimer's disease.

That study began early this year at Washington University School of Medicine in St. Louis. It is being supported by DIAN, a U.S.-funded collaboration of leading Alzheimer's disease centers worldwide.

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