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Despite two failed late-stage trials of its experimental Alzheimer's drug solanezumab, Eli Lilly and Co said on Friday it plans to run yet another study, this time focusing only on mild patients who appeared to respond to the treatment. And the company will take extra steps to ensure it is testing actual Alzheimer's patients by pre-screening them with its imaging agent Amyvid to ensure they have deposits of the protein beta amyloid that is linked with the disease.
Solanezumab, which patients take by infusion, works by blocking the beta-amyloid protein that forms plaques in the brain, signalling the onset of the disease. Bapineuzumab, a similar drug developed by Pfizer Inc, failed its main trial goals last year. Lilly's two earlier trials of solanezumab had involved patients with mild to moderate symptoms. Combined data from those trials last summer 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.
New trial
Lilly said the new Phase III trial 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. "Since Lilly saw a signal of benefit in the mild patients in the completed trials, it makes a lot of sense for them to simply zoom in on that group in this new trial," said Steven Ferris, director of the Alzheimer's Disease Center at NYU Langone Medical Center in New York. "It's a roll of the dice again, but they'll get a definitive answer."
Ferris said Lilly's decision to forge ahead with another trial was a bold move, but one worth taking because no current treatments slow progression of the disease. "That's what we need." 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. An estimated 5 million Americans have Alzheimer's, the most common cause of dementia.
More than 38 million people worldwide are believed to have dementia, including Alzheimer's disease, and those numbers are expected to rise as more people live longer.
Based on symptoms
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 addition to using Amyvid, its new radioactive imaging agent, Siemers said the company will also look if biochemical measures in the spinal fluid can also help assess whether patients have Alzheimer's. "This pre-screening will take Lilly longer to enrol patients, but is a wise move," Sanford Bernstein analyst Tim Anderson said in a research note. He said the earliest the drug is likely to reach the market, assuming the trial succeeds, is late 2017.
Maria Carrillo, vice president of scientific and medical affairs for the Alzheimer's Association, said the tighter screening will "strengthen" the new study. "When you're using an amyloid-based approach you want to make sure amyloid is there."
Setbacks
Lilly's renewed push behind solanezumab comes amid other recent setbacks for its Alzheimer's program. Last month Lilly halted a mid-stage study of a different type of Alzheimer's treatment, from a class known as beta secretase, or BACE, inhibitors, after signs of potential liver toxicity. But the company said it remains interested in developing other BACE inhibitors.
Earlier this month, the US Centers for Medicare & Medicaid Services proposed guidelines that would deny reimbursement for Amyvid unless patients are taking part in one of several clinical trials in which the $3 000 test is being used.
In the meantime, two independent studies of solanezumab are just getting off the ground, and could shed further light on the drug's potential. They involve a study of elderly patients who do not yet have symptoms of Alzheimer's but who have deposits of amyloid in their brains, and a study of patients with an inherited high risk of developing Alzheimer's.
