SAN DIEGO — It was Biogen's best pitch yet. The company offered up more data, new hunches and a panel of experts to try to explain why its experimental drug for Alzheimer's disease works.
But if the goal was to sway opinion, the biotech giant didn't appear to change many minds.
Biogen's drug, named aducanumab, had split the Alzheimer's research community in the months leading up to Thursday's presentation. Two large clinical trials testing it in patients with less advanced disease looked negative after early analyses, leading the company in March to stop them before they finished.
Then, in a rare about-face, Biogen announced plans to submit aducanumab for approval based on a newer, larger dataset that showed one of the studies actually succeeded. Detailed data supporting that decision were presented Thursday at a research conference known as CTAD.
CTAD could have provided a forum for Alzheimer's doctors and researchers to get on the same page, like it had done in past years, according to University of Kentucky neurology professor Gregory Jicha. So far, however, the only consensus about aducanumab is that one hasn't been reached.
"It's amazing to me how the data really has polarized the scientific community," Jicha said.
Much of the divide stems from the two large, identically designed aducanumab studies having such divergent results. The one Biogen billed as successful found patients experienced significantly less decline on a cognitive test when given high doses of Biogen's drug as opposed to placebo. The unsuccessful one found the opposite, with patients given placebo performing better than those on the high dose.
At CTAD, the company said the high-dose patients in that study were better able to perform certain day-to-day activities. They also showed a 0.4-point lower decline on the 18-point cognitive test, the trial's main measure of success. On safety, just over a third of high-dose patients across both trials experienced a type of brain swelling as a side effect, while about 18% had micro-hemorrhages.
Biogen claims the side effects were mostly mild and manageable, and that the efficacy differences were due to the positive trial having more patients who got the full course of high-dose aducanumab. These explanations and the data behind them have been met with mixed reactions, though some are withholding final judgments until even more results become available.
"Despite the fact that the findings aren't definitive, I'm encouraged by the results that have been presented," Eric Reiman, executive director of the Banner Alzheimer's Institute, said in an interview.
Constantine Lyketsos, a psychiatry and behavioral sciences professor at Johns Hopkins Medicine, is less encouraged. He said he doesn't think aducanumab can get approved on its efficacy data and, if it did, he still wouldn't feel comfortable giving it to patients for multiple years because of safety concerns.
"What's really striking to me," Lyketsos told BioPharma Dive, "is the study that didn't work is way off in terms of its effect size compared to the one that worked. The only similar finding they have is that everyone gets worse."
Jicha, from the University of Kentucky, said Biogen's presentation made him a little more positive on aducanumab than he was heading into the conference. Though his views remain "middle ground," he now believes the drug deserves more investigation.
"I was very negative and uncertain, and really thought it was just a lot of hype to move stock market prices rather than any true finding that would help patients," he said. "The fact that the data sway me, again, comes all back to the impact on patients' daily living."
Biogen's challenge remains convincing a larger portion of the research community, as well as the Food and Drug Administration, that the potential rewards of aducanumab treatment outweigh the risks.
To do this, the company likely needs a better way of illustrating that the small improvement in cognitive test scores translates to benefits for patients. The panel that spoke after Biogen's presentation — which, notably, included scientists who worked on aducanumab trials or received grants or consulting fees from the company — vouched that such a correlation exists, but many want more proof.
"We've continued to focus on a cognitive change when, in fact, there seem to be very important data in the functional scale that was used. But there are details that I'm sure will be coming," said Jeffrey Kaye, director of the Layton Aging and Alzheimer's Disease Center at the Oregon Health & Science University.
"Unfortunately, as the different datasets get cut into smaller and smaller groups, it's harder and harder to make more definitive statements."
Biogen's argument, along with the series of assumptions and calculations that led to its decision to file aducanumab for approval, could have lasting effects on Alzheimer's drug research.
At least for now, one of those effects is a research field divided.
"The people (like me) who were doubtful (or worse) that they had enough to make a case for FDA approval remain doubtful," wrote chemist and well-known industry commentator Derek Lowe in a Science column published Friday, the day after Biogen's presentation. "And the people (there are some) who think that it's approvable haven't changed their minds, either, from what I can see."