Indication: Alzheimer’s disease
Sponsors: Biogen, Eisai
A few weeks ago, Biogen and Eisai’s Alzheimer’s disease candidate aducanumab would have been right at the top of the list of failed 2019 trials. But that would have been before the surprise announcement that the project hadn’t been canned after all.
In March, aducanumab—which targets soluble amyloid—flunked a futility analysis of the ENGAGE and EMERGE trials ahead of the planned readout in 2020. The partners said they were pulling the studies, all but halting development of the drug. That hit their share prices hard, as investors lost any hope that aducanumab might rescue the nearly dead amyloid hypothesis of Alzheimer’s disease.
Then in a massive surprise, Biogen announced in October that they’d got it wrong. The futility analysis was incorrect, and not only was the program back on track, but the interim data was strong enough to allow it to ask the FDA to approve the drug.
So, if all is back on track, why is aducanumab included in this listing? For one thing, there’s a worrying discrepancy between the two phase 3 trials. A statistically significant improvement on a clinical dementia scale was seen in patients in the EMERGE study who received the high dose of aducanumab, but in ENGAGE, placebo numerically outperformed high-dose aducanumab on that scale as well as a test of cognitive function.
One analyst at least is entirely unconvinced by Biogen’s optimistic decision to go ahead with a regulatory filing for aducanumab. Baird analyst Brian Skorney thinks there’s practically no chance of approval, given that “the FDA standard of approval is substantial evidence of efficacy and the cumulative data for aducanumab falls really far of this standard.”
Biogen remains bullish on the new data, insisting it represents the first time that any drug has been able to show a statistically significant improvement on a clinical dementia scale. Whether it’s right or not will depend on convincing the FDA that the unmet need in Alzheimer’s warrants approval on weak data.
Despite aducanumab's resurrection, there is still a sense that confidence in the amyloid hypothesis of Alzheimer’s disease treatment has been all but exhausted, with attention turning to earlier-stage projects targeting other potential disease targets such as tau pathology and microglial cells.