Drug slowing Alzheimer’s dementia unexpectedly moves to FDA submission
In a stunningly unusual turn of events a new Alzheimer’s drug, previously declared a failure back in March, has been resurrected with the pharmaceutical company behind the treatment suggesting the earlier decision to discontinue the research was premature and based on incorrect data analysis.
Biogen’s decision to immediately discontinue human trials for a promising Alzheimer’s drug called aducanumab came on the heels of several other big research failures into drugs designed to slow, or even reverse, neurodegeneration and cognitive decline. At the time the company suggested an independent data monitoring committee had evaluated early results from two large, global Phase 3 human trials and concluded they were failing to meet primary efficacy endpoints.
This new announcement from Biogen suggests that earlier data analysis, called a futility analysis, may have been premature and more recent study of larger datasets from one of the two Phase 3 trials has revealed significantly successful results. Biogen is claiming as the trials progressed, and concerns over side effects dissipated, more patients were exposed to higher doses of aducanumab. The early independent analysis of the trial data apparently only evaluated data gathered up to December 2018, but the trials continued until March 2019. Examining those extra months of data revealed patients receiving longer exposure to higher doses displayed significantly slower rates of cognitive and functional decline compared to the control group.
“I have to pinch myself because I almost don’t believe it yet,” said Al Sandrock, head of research and development at Biogen, in an interview with STAT. “In retrospect, the results of the futility analysis was incorrect. That’s because it was from a smaller dataset that looked at patients with less exposure to high dose aducanumab.”
The death of aducanumab back in March widely signaled the broader failure of treatments designed to target amyloid-beta plaques, the toxic protein aggregations commonly thought to be the cause of Alzheimer’s-related neurodegeneration. Years of clinical trial failures had suggested drugs designed to clear these toxic protein accumulations were not resulting in meaningful clinical improvements for patients with moderate to severe Alzheimer’s. However, this new announcement has, for some, rekindled hope for the fledgling amyloid hypothesis.
“It is encouraging for the field that the tremendous work delivered to target amyloid beta appears to be validated in this trial and we should now redouble our efforts to tackle this central problem in Alzheimer’s Disease, alongside other important contributors,” says Bart De Strooper, from the UK Dementia Research Institute.
A statement from the Alzheimer’s Association, based in Chicago, also indicated optimism at the latest Biogen announcement. The statement noted the team from the Alzheimer’s Association, “have never been as optimistic as we are today.”
Not everyone is confident this resurrection of aducanumab will lead to a clinically meaningful new Alzheimer's drug. Nikolaos Robakis, a skeptic of the amyloid hypothesis and neuroscientist at the Icahn School of Medicine at Mount Sinai in New York City was quoted as saying, “Why [Biogen] came back now and said they would pursue what before they themselves they tried to discard – it seems, to me, strange.”
Biogen has yet to release comprehensive data from its two Phase 3 trials but it says this decision to resurrect the drug and move it to market approval came from consultations with the FDA. The current plan is to file an application with the FDA in early 2020. If aducanumab is ultimately approved it will be the first drug to reach the market to treat cognitive decline in the early stages of Alzheimer’s disease.