Roche on Thursday announced the disappointing trial results of its Alzheimer's drug crenezumab—but some experts say "[t]his is by no means the end of the story."

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Details on the trial

For the trial, Roche, Banner Alzheimer's Institute, and the University of Antioquia in Colombia enrolled 252 people to determine whether crenezumab—a drug designed to counter amyloid beta protein accumulation in the brains of Alzheimer's patients—would slow or halt the disease.

The researchers identified extended families of people who had a rare genetic mutation that nearly guarantees the person will develop Alzheimer's disease early, typically when they reach their mid-40s. However, the individuals included in the trial had not yet developed Alzheimer's symptoms.

Those with the mutation were randomly assigned either a placebo or crenezumab. The researchers also created another placebo group of people without the genetic mutation. The phase 3 trial has been running for more than a decade.

Roche and Banner announced that, while there were some small differences in tests measuring cognitive abilities in the participants that favored crenezumab over a placebo, none of them were statistically significant. The drug ultimately did not slow or prevent cognitive decline among those at significant risk for developing the disease.

"We're disappointed that the treatment did not demonstrate a statistically significant clinical benefit," Eric Reiman, executive director of the Banner Alzheimer's Institute, said. "At the same time, we're proud of the impact that this precedent-setting trial has had in shaping a new era in Alzheimer's prevention research and we're extremely grateful to our research participants and their families."

Reaction

Stephen Salloway, a professor of neurology and psychiatry at Brown University, said the results of the trial are disappointing.

"I don't want to throw the baby out with the bathwater because one drug with one particular target is ineffective," he said, adding that researchers are awaiting results from other, larger studies evaluating other drugs that target amyloid beta proteins.

Similarly, Pierre Tariot, from Banner Alzheimer's Institute, said more research is needed to determine whether escalating dosages of crenezumab made a difference in the patients, which requires analysis of brain scan changes and changes in the fluid surrounding the brain and spine.

"This is by no means the end of the story," Tariot said.

Randall Bateman, a professor of neurology at Washington University, said researchers are still interested in the results from the study because crenezumab was administered before memory and thinking problems began for many patients. Researchers will want to look at the data to determine whether crenezumab affected different amyloid markers like plaque build-ups or tau proteins, which are also found in Alzheimer's patients.

"The question really is would it be more effective if we go earlier?" Bateman said. "I think there's biological reasons to believe it will, but to date, we don't have any evidence of that."

Other experts said researchers need to start taking a broader approach to Alzheimer's and better understand what role aging plays in the disease.

"I think we need to manage our expectations," said Howard Fillit, co-founder and chief science officer at the Alzheimer's Drug Discovery Foundation. "It's becoming increasingly clear that aging is the leading risk factor for Alzheimer's disease, so we need to apply our understanding from 100 years of research."

Francisco Lopera, a neurologist in Colombia who helped lead the study, said the trial convinced him that "prevention is the best way of looking for the solution for Alzheimer's disease, even if today we don't have a good result."

"We know that we did a big step in the contribution to the investigation of Alzheimer's disease," he said. "And now we are prepared to start other steps in looking at the solution for this disease." (Alltucker, USA Today, 6/17; Belluck, New York Times, 6/16; Bettelheim, Axios, 6/17; Feuerstein, STAT+ [subscription required], 6/16)