Biogen’s Alzheimer’s Reveal: “A Major Advance for the Field” Despite Mixed Results
At long last, Biogen presented full data today on its Alzheimer’s drug aducanumab at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) conference held in San Diego. The data was presented by Samantha Budd Haeberlein, vice president of Clinical Development for Biogen.
In March, Biogen and its collaboration partner, Tokyo-based Eisai, announced they were discontinuing the global Phase III trials, ENGAGE and EMERGE, of aducanumab in patients with mild cognitive impairment from Alzheimer’s, as well as the EVOLVE Phase II trial and the long-term extension PRIME Phase Ib trial. An independent data monitoring committee indicated the trials were unlikely to hit their primary endpoints in a futility analysis.
But in late October, the companies announced that after discussions with the U.S. Food and Drug Administration (FDA), and further analysis of the data, they were going to pursue regulatory approval for the drug. The Phase III EMERGE trial met its primary endpoint, showing a significant decrease in clinical decline. The company believes that data from a subset of patients that were given a high enough dose of the drug had significant benefits on measures of cognition and function, including memory, orientation, and language, as well as benefits on activities of daily living.
Haeberlein emphasized that when the futility study was conducted on the EMERGE and ENGAGE studies, only about half of the patients had the opportunity to finish their Week 78 visit. The bottom line was that a much smaller percentage of patients in the trial had received their full and complete dosages at the highest dose levels at the time of the futility analysis.
“After futility analysis,” Haeberlein said, “a larger data set became available. That larger data set showed a different outcome from futility and formed the basis of the difference between futility and the difference between the two studies.”
And it was only very recently, because of a database lock, that Biogen could run a final analysis on the complete dataset. It’s the final dataset that is the basis for regulatory submission.
The conclusion of the full topline results was that in EMERGE, high dose aducanumab decreased clinical decline on the primary and secondary endpoints. In ENGAGE, aducanumab did not reduce clinical decline, but in post hoc analysis, data from a subset of patients exposed to high dose aducanumab support the positive findings of EMERGE.
Also, in smaller sub-studies, Haeberlein noted, “aducanumab showed an effect on disease-related biomarkers.”
The most common adverse events were amyloid-related imaging abnormalities (ARIA), particularly ARIA-E, which refers to cerebral edema.
The company is finalizing details of a re-dosing study with a goal of offering access to aducanumab to eligible patients who were previously enrolled in the aducanumab clinical studies.
Paul Aisen, director of the Keck School of Medicine of USC’s Alzheimer’s Therapeutic Research Institute, who was on a panel responding to the presentation, said, “The data is complex. I think the futility interpretation was unfortunate. But the primary analysis of EMERGE is positive and the analysis of all the key secondaries was consistent and positive. And as important, the biomarker reports the mechanisms of significant amyloid reduction leading to decreased tauopathy… I think that is a hugely important result and represents a major advance for the field.”
Aisen went on to say, “The ENGAGE data set, the results of the final analysis are negative. This is challenging. But when we consider the difference in timing of enrollment … I think the data from ENGAGE and EMERGE can be considered consistent. So, I think we are left with an overall positive interpretation of the data from the aducanumab studies that therefore represent a truly major advance for the field.”