The stakes are high for aducanumab because it’s among the last potential drugs standing that targets beta amyloid, the protein that forms sticky plaques around neurons in the brains of people with Alzheimer’s.
But the failure of several anti-amyloid drugs in large clinical trials has suggested plaque buildup might be the wrong target to stop the disease’s progression once people show symptoms.
Still Biogen and its partner, Tokyo-based Eisai, had high hopes for aducanumab, which binds to and eliminates forms of amyloid thought to be particularly noxious. An early clinical trial confirmed the drug was a powerful plaque buster. In 2015, the companies launched two large, identically designed clinical trials, known as ENGAGE and EMERGE, each testing two different doses of aducanumab against a placebo in more than 1600 people with early-stage Alzheimer’s and confirmed amyloid buildup in the brain.
At the Clinical Trials on Alzheimer’s Disease congress this week, Biogen has announced that they are moving forward with requesting FDA market approval of their experimental Alzheimer’s drug that it had declared a failure 7 months earlier. They claim that data from their clinical trials was not calculated with enough of the later data from a subset of the participants, and that the late data showed a better outcome than had been initially calculated.
Changes made during the study and unusual analyses of the data made the results hard to interpret. And the newly released results showed the drug made only a very small difference in thinking skills in one study and none in the other.
“ broken all the rules, really, about how you analyze data and report it.” says Professor Rob Howard, a psychiatrist at University College London who has run clinical trials of potential Alzheimer’s treatments. More positive results from a subset of patients that weren’t preselected at the trial’s launch are not convincing.
“It’s hard to know exactly what happened here,” said Dr. Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation. “I don’t see how the FDA could approve it.” The drug did not reverse decline, only slowed the rate of it compared to the placebo group by 22% in one study. Yet that meant a difference of only 0.39 on an 18-point score of thinking skills. “It’s a very small amount,” Fillit said.
Other researchers, like Paul Alan Cox, PhD, Executive Director of the Institute for EthnoMedicine’s Brain Chemistry Labs and his team of scientists, argue that amyloid and tau are symptoms rather than causes of the disease and instead seek cures in the mechanisms of protein misfolding.
Still, Alzheimer’s patients and families are desperate for any help, no matter how small, adding pressure on the Food and Drug Administration to approve something. Maria Carrillo, PhD, chief science officer at the Alzheimer’s Association, said it was “the largest reduction that we’ve seen to date,” adding, “It may mean that they remember their loved ones a little longer.” The drug “is worthy of significant, rigorous exploration” and review by the FDA, she said. “This is an important moment for the Alzheimer’s community.”