The meeting that could change Alzheimer's treatment.
Alzheimer's disease research faces one of its most pivotal moments this week.
The disease, which affects millions of patients and families, remains notoriously difficult to treat, having thwarted every effort by the world's most powerful pharmaceutical companies to slow or stop its progression. But over the last year, one drug meant to change the course of Alzheimer's has come within striking distance of approval.
Its biggest hurdle yet comes Friday, when a panel of experts tasked with evaluating new treatments for brain diseases will convene, and by the end of the day make a recommendation to the Food and Drug Administration about whether or not to approve the drug, called aducanumab. Though the FDA doesn't have to follow such recommendations, it usually does.
The months leading up to this meeting have been marked by intense debate as doctors, researchers and patients weigh the pros and cons of aducanumab becoming available. A positive opinion from the committee, followed by a green light from the FDA, would help address a desperate need for new Alzheimer's medicines.
Such an outcome could be a "shot in the arm" for Alzheimer's research, according to Eric Reiman, CEO of the Banner Alzheimer's Institute. The most recent treatment to be approved came in 2003, for a combination drug that helps with memory but not the underlying cause of the disease.
It would also be a much needed win for the drug's developer, Biogen, validating a risky decision to bet heavily on aducanumab while competitive threats chip away at its business.
Yet, some fear an approval could have unintended, negative consequences. Drugs that work in the same way as aducanumab have failed again and again in clinical testing, prompting questions — and, at points, criticism — about whether time and resources would be better spent investigating other potential therapies.
There are concerns, too, that aducanumab might not actually be effective, or effective enough to bring substantial improvements to patients' daily lives. If those doubts persist, aducanumab could be met with pushback from the regulators reviewing it and the insurance companies deciding how to cover it, which then might put added obstacles in front of patients looking to access what would likely be an expensive drug.
"I would love to see an effective therapy approved," said Michael Sherman, chief medical officer for the New England-based insurer, Harvard Pilgrim. "But I think there is also skepticism, given the general history as well as the background with this drug, about whether it will be approved and to what degree it will be efficacious."
The skepticism surrounding aducanumab stems from two large clinical studies that were supposed to show it works as intended.
The studies, titled EMERGE and ENGAGE, were identically designed. Each enrolled over 1,600 patients with early Alzheimer's disease, and tested a low dose and a high dose of aducanumab against placebo to see whether patients performed better on a cognitive test after a year and a half of treatment.
By March 2019, an independent committee that was monitoring the studies had concluded neither was likely to succeed, leading Biogen to stop them early. Aducanumab, it seemed, would join the long list of Alzheimer's drugs shelved after too many setbacks.
But then, seven months later, Biogen made an unprecedented reversal. The company announced it would submit aducanumab for approval after additional analyses with more data showed EMERGE had actually succeeded, with patients on the high dose performing significantly better than those in the placebo arm.
ENGAGE, though still a negative trial after further analysis, had data that supported the findings in EMERGE, Biogen claimed.
The company would later propose one possible reason for two almost identical studies having such divergent results: that EMERGE had more patients who were on the high dose for longer amounts of time. Researchers who spoke to BioPharma Dive said that theory is plausible.
Still, Biogen's analyses and the various tweaks made to its studies have raised serious doubts about the reliability of the data. Stakeholders expect the company's defense to be a point of discussion at Friday's meeting.
"You have one positive trial, and you have another trial that's a little bit more difficult to interpret. And I think that's what the committee is really going to have to deal with: how to interpret that ENGAGE trial," said Howard Fillit, chief science officer of the Alzheimer's Drug Discovery Foundation.
In the meantime, the Alzheimer's community remains split on the aducanumab data and Biogen's rationale for pursuing approval. Analysts at the investment bank Stifel recently wrote there's a "significant binary divide" among the experts they've spoken to, with some viewing EMERGE as positive and others taking a more cautious stance.
Importantly, Biogen has had only limited success convincing people that the cognitive test results seen in EMERGE can translate to a noticeable benefit on patients' daily lives.
"The value is less about how you score on a cognitive test, and more what it means for people's ability to function," Sherman of Harvard Pilgrim said. "And if we don't get data on that, it's going to make the discussion around how to cover this — what to pay for, and under what circumstances — that much harder."