Biogen Reverses Course on Alzheimer’s Drug Analysis, Plans FDA Filing

Xconomy Boston — 

Six months after Biogen stopped work on a closely watched experimental Alzheimer’s disease treatment, the neuroscience drug developer is reviving it with plans to file for FDA approval.

Aducanumab’s Phase 3 failure in March was viewed as yet another nail in the coffin for the so-called “amyloid hypothesis”—the theory that by breaking up or clearing the buildup of amyloid protein in the brain, a therapy could stop or even reverse the course of patients’ memory loss.

But on Tuesday Biogen (NASDAQ: BIIB) and Japan’s Eisai, which have been collaborating to advance the drug as a potential treatment for early Alzheimer’s disease since October 2017, announced plans to ask the FDA to review the drug early next year. The company said the change in course was made after conversations with the agency.

Cambridge, MA-based Biogen said it changed its mind about advancing the drug after looking at a larger dataset than the one used in March. Biogen said its initial analysis was incorrect. It added that data in the new analysis show that aducanumab did remove amyloid and patients treated with the drug showed improvements in measures such as memory, orientation, and language, according to an assessment scale.

The company attributes the changes to data from a larger number of patients who were treated with a high dose of the drug. The data come from two parallel studies, called “Emerge” and “Engage.” However, only the Emerge study met the main goal of reducing clinical decline. The company said it thinks that data on a subset of patients in Engage who received high doses of the drug supported the results from Emerge.

Howard Fillit, the founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation in New York, says he feels “cautiously optimistic” about Biogen’s new data, but he added that the company has left a number of unanswered questions.

“They showed improvement on cognitive and function in a statistically significant way, which was pretty impressive,” Fillit says. “It’s certainly encouraging the way they’ve analyzed it. But it is hard to understand why ‘Emerge’ succeeded and ‘Engage’ didn’t have any statistically significant result.”

He also says it’s impossible to know what exactly the company and the FDA discussed—and difficult to determine the application’s chances of approval.

“I don’t think we really know what went on in that discussion … and ultimately, whether they’ll approve it based on, really, one trial, and then some pooled data, which is often very tricky to do,” he said.

SVB Leerink analyst Geoffrey Porges echoed that sentiment in a research note: “This could range from ‘the agency has reviewed all the data with us and has guaranteed approval’ to ‘you can file whatever you want and we’ll review it.”

Drug companies have struggled mightily to develop treatments for Alzheimer’s, burning billions of dollars in the process.

Just five weeks ago, Biogen and Eisai pulled the plug on another experimental Alzheimer’s drug. That treatment, elenbecestat, blocks the enzyme beta secretase 1 (BACE1), which helps turn the protein amyloid beta into sticky plaques in the brains of Alzheimer’s patients. Part of a class of drugs called BASE inhibitors, the companies ended the study after independent reviewers concluded that its risks to patients were greater than its benefits.

Biogen licensed aducanumab from Neurimmune, a Swiss biotech, in 2010. Shares of Biogen rose 26 percent Tuesday on the latest news for the drug, closing at about $282 apiece. In March, before it stopped the aducanumab trials, Biogen’s stock price was about $320.

Biogen plans to release more details about its new findings in December at the Clinical Trials on Alzheimer’s Disease meeting in San Diego.