Eli Lilly and Co. said it will test its experimental Alzheimer’s drug in patients with early stages of the disease after the medicine failed to slow the condition in more advanced patients.
The trial of 2,100 patients, called Expedition III, will use new measures of cognitive function, such as the ability to do tasks like cooking or driving, or remembering words after a delay. It’s meant as a more-targeted, more-sensitive trial than two earlier ones that had a wider range of patients, said Eric Siemers, a senior medical director at Indianapolis-based Lilly.
Lilly is pushing ahead with the drug, called solanezumab, in an effort to gain the first medicine approved that treats Alzheimer’s causes rather than just the symptoms. The therapy targets the buildup of plaque known as beta amyloid in the brain that’s thought to be a basis of Alzheimer’s. Clearing or preventing it may help slow or halt progression of the disease, though that theory hasn’t been proven.
“Since we saw the signal in the mild patients,” in the earlier trials, “we’re restricting the patient population,” Siemers said in an interview. The trial should take about 22 months to complete, he said in a conference call Friday.
The company will also use new tests for biological signs of the disease to help enroll patients and see whether their illness is advancing.
By testing people for evidence of the brain plaques that are thought to be a cause of Alzheimer’s, Siemers said the company can avoid accidentally enrolling patients who have some other form of cognitive impairment and wouldn’t be affected by solanezumab.
More accurate
“The technology wasn’t available to test during Expedition I and II, but now we can for every patient going into the trial,” Siemers said. “It’s just better medicine, we have a more accurate diagnosis and a treatment that targets it.”
More than 5 million Americans have Alzheimer’s, the most common form of dementia, and the number is expected to surge to as many as 16 million by 2050 as the population ages, according to the Alzheimer’s Association. No drugs currently on the market have been shown to slow progression of the disease.
The market for medicines may be worth $20 billion annually, Deutsche Bank estimated last year. Merck & Co., Novartis AG, Roche AG and other large drugmakers are pursuing treatments. A final-stage trial of bapineuzumab, a drug developed jointly by Pfizer Inc., Johnson & Johnson and Elan Corp., failed last year after it didn’t show a benefit.
Beta amyloid
Lilly and other drugmakers have struggled to show that success in affecting beta amyloid translates into clinical improvement in patients. It’s possible that the patients in previous trials were treated too late, after damage from the disease was already done. Or it could be that beta amyloid is the wrong target. Sanofi, the Paris-based drugmaker, has said it won’t start developing an Alzheimer’s treatment until more is known about the causes of the disease.
Lilly said in December that it planned to go ahead with a third Phase III trial of the drug, after two other final-stage trials showed that solanezumab slowed progression of the disease in people with a mild form of the disease. Drugs typically require three stages of testing before approval. In an analysis of the first two Phase III trials, solanezumab slowed memory loss and cognitive decline by about 30 percent in early-stage patients, researchers said.
“Clinicians feel that’s clinically meaningful,” Siemers said. “That’s an effect we think would be worthwhile in clinical practice.”
Expedition III will be run in 11 countries, with about two-thirds of the patients in the United States. The rest will be in Japan, Australia and Europe, Siemers said.
