Reuters reports that the turnaround was built on “top secret” meetings, non-disclosure agreements and six months of researchers, regulators and statisticians churning the data on a larger dataset that included a total of 3,285 patients.
Earlier this week, Biogen stunned everyone by announcing that analysis of a large dataset from several of its clinical trials of aducanumab in Alzheimer’s patients were positive. This came after an announcement in March that the company and its collaboration partner, Tokyo-based Eisai, were basically abandoning the program after an independent data monitoring committee indicated the trials probably wouldn’t hit their primary endpoint.
Reuters reports that the turnaround was built on “top secret” meetings, non-disclosure agreements and six months of researchers, regulators and statisticians churning the data on a larger dataset that included a total of 3,285 patients.
The two trials, EMERGE, which evaluated 1,638 patients, and ENGAGE, which evaluated 1,647 patients, were discontinued after the futility analysis on March 21, 2019. That analysis was based on data prior to December 26, 2018 in 1,748 patients who’d completed the 18-month trial period. The analysis found the studies were not likely to meet the primary endpoint.
After ending those studies, a larger dataset that included a total of 3,285 patients became available. Of them, 2,066 patients had completed the full 18 months of treatment. The companies analyzed the data, and found it contradicted the futility analysis.
Basically, in EMERGE, patients receiving the high dose of aducanumab were observed to have a significant reduction of clinical decline from baseline in CDR-SB scores at 78 weeks of 23% compared to placebo. They also showed a consistent decrease of clinical decline for the pre-specified secondary endpoints, including the Mini-Mental State Examination, 15% compared to placebo, the AD Assessment Scale-Cognitive Subscale 13 items of 27% compared to placebo, and the AD Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version, 40% compared to placebo.
Also, imaging of amyloid plaque deposits in EMERGE showed that the plaque burden was decreased with low and high dose aducanumab compared to placebo at 26 and 78 weeks. Biomarker data of tau levels, another abnormal protein linked to Alzheimer’s disease, was also found to be reduced in the cerebrospinal fluid, which supports the clinical findings.
The findings were so surprising internally compared to what the independent data monitoring committee had concluded that Biogen did not share the new findings with their own trial investigators and oversight committee. Biogen also pulled in outside Alzheimer’s experts and statisticians to analyze the new findings and discussed what they were seeing with FDA officials.
In consultation with the FDA, the company now plans to submit the drug for approval next year. The company, which had lost $18 billion in market value overnight when the programs were canceled, found that company shares rebounded 27% this week.
As promising as the news is, analysts are proceeding with caution. Sumant Kulkarni, analyst with Canaccord Genuity, wrote, “…this news, in our view, means the fear of missing out component is firmly back to occupy investor mind share as the multi-billion AD market is simply too large to ignore. We acknowledge these data present some hope for the AD community and opportunity for investors. But, we would like to wait until Biogen presents a full data set at the Clinical Trials in Alzheimer’s Disease (CTAD) conference in San Diego, California (December 4-7) before we may be able to recommend a more active position.”
Apparently, Biogen worked closely with the FDA and met with them twice before deciding to move forward with a submission plan. Biogen officials told Reuters that the final decision was made immediately after the second meeting.
For the FDA “to say it’s reasonable to file an application after two extensive discussions with them, formal meetings as well as a number of informal discussions, I think it’s significant,” Alfred Sandrock, Biogen’s executive vice president, Research & Development and chief medical officer, told Reuters.
Eisai, in March, had decided to continue working on a second drug, BAN2401. Now, Eisai and Biogen hope that the aducanumab news will re-energize the BAN2401 trial. Like with the aducanumab studies, the highest doses of BAN2401 showed some encouraging data in a Phase II trial last year.
“That’s why in the Phase III trial, we are only studying the highest dose,” Ivan Cheung, Eisai’s chief executive officer, told Reuters.
