2016-11-23 22:59:18
Eli Lilly’s Experimental Alzheimer’s Drug Failed in Large Trial

An experimental Alzheimer’s drug that had previously appeared to show promise in slowing the deterioration of thinking and memory has failed in a large Eli Lilly clinical trial, dealing a significant disappointment to patients hoping for a treatment that would alleviate their symptoms.

The failure of the drug, solanezumab, underscores the difficulty of treating patients who have reached the point of showing even mild dementia, and supports the idea that by that time the damage in their brains may already be too extensive. And because the drug attacked the amyloid plaques that are the hallmark of Alzheimer’s, the trial results renew questions about a leading theory of the disease, which contends that it is largely caused by amyloid buildup.

No drug so far has been able to demonstrate that removing or preventing the accumulation of amyloid translates into a result that matters for patients: stalling or blocking some of the symptoms of dementia.

“It’s not going to be disease-modifying therapy for mild patients, so that’s heartbreaking,” said Dave Ricks, the incoming president and chief executive of Eli Lilly.

There are clinical trials underway with several similar drugs made by other drug companies. And two large trials are in the works with solanezumab. Experts said Wednesday they are still holding out hope for those studies because most involve people who are at high risk for Alzheimer’s but do not display symptoms.

Some Alzheimer’s experts said they were not surprised by the outcome of the trial, which they said reflects an emerging scientific understanding of Alzheimer’s as a disease with a complex set of causes that begins damaging the brain so many years before people show symptoms that a drug given to people with even mild dementia may have little chance of success.

“Once you see amyloid on a scan, it’s probably been there for decades,” said Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai Hospital who is not involved in trials involving anti-amyloid drugs.

“I’m worried and have been worried that that’s just too late” for a drug that removes amyloid to meaningfully treat symptoms of a disease that has been progressing for years, he said. “I think it has a better chance of working much earlier.”

But, he said, testing a drug before people have begun showing symptoms is challenging and costly. Such trials need to involve even larger numbers of patients to produce a useful result.

Solanezumab had previously failed in two large clinical trials involving patients with mild or moderate Alzheimer’s disease. But when Lilly reported the results of those trials in 2012, the company said that the drug did have an effect in a subset of patients with mild symptoms. So it started another trial with 2,100 patients with mild dementia caused by Alzheimer’s.

In a news release on Wednesday, the company said that although some of the effects looked promising, “patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo.”

Dr. Eric Siemers, distinguished medical fellow at Lilly, said in a press briefing later Wednesday morning: “This outcome is not what we had hoped for and we are disappointed for all the patients waiting for a treatment for Alzheimer’s disease. We had hoped that solanezumab would be the first.”

In the company statement John C. Lechleiter, Lilly’s chairman, president and chief executive officer, said “We will evaluate the impact of these results on the development plans for solanezumab and our other Alzheimer’s pipeline assets.” The company said it no longer planned to seek regulatory approval for use of the drug in treating symptomatic patients.

The results are yet another setback in the decades-long effort to find a treatment for Alzheimer’s, a condition that afflicts about five million Americans.

“This is very disappointing,” said Dr. Reisa Sperling, a neurologist who is recruiting patients for a planned trial to see if solanezumab can help people with amyloid plaques who are about 10 years away from having any Alzheimer’s symptoms. “But I have to be honest that I’ve always thought we needed to treat much earlier because by the time people have mild dementia, they already have a lot of irreversible damage,” she said.

The trial she is leading, called A4, had hoped to reach its goal of about 1,150 patients and be able to start the trial by the middle of next year, said Dr. Sperling, who directs the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital.

Dr. Sperling said a silver lining was that in the Lilly trial, the patients taking solanezumab did show improvement, just not enough to be statistically significant.

“Although I’m very disappointed, and I have several patients within my practice who were hoping to take this drug,” she said, the Lilly results “all moved in the right direction, which is great, but the magnitude of the differences are small.”

She said she plans to evaluate the data and try to understand if changes should be made to the design of the A4 trial. “What does that mean for an earlier population? Do we need more people? Do we need a longer time? I just want to get a clear result.”

She added, “I’m sorry for the field, but I hope that it won’t deter us from keeping to work to find a solution because we have to.”

Eli Lilly stock initially dropped after the news this morning. Stocks of Biogen and Merck, which are also developing similar drugs, dipped.