1. Aducanumab

biogen
Biogen and Eisai are set to find out in June whether their Alzheimer's med aducanumab wins FDA approval, three months after its original decision deadline.

Drug: aducanumab
Companies: Biogen and Eisai
Used for: Alzheimer's disease
Est. 2026 sales: $4.8 billion

No other pending drug approval faces more skepticism on one hand, and more cheerleading on the other, than Biogen’s anti-amyloid beta antibody aducanumab for Alzheimer’s disease.

On one side are hopeful Alzheimer’s patients and families, advocates, the drugmaker and some devotees inside the FDA. Their argument is that a stake in the ground for Alzheimer’s is needed, and while aducanumab may not be a wonder drug, at least it’s a start.

On the other side are physicians, other drugmakers with Alzheimer’s candidates and the most of the FDA advisory panel that reviewed aducanumab—experts who said they understand the desperate need for a solution, but that the drug just doesn’t work well enough to make a difference for Alzheimer’s patients.

Aducanumab flopped its November AdComm with scathing testimony and a resounding 8-1 thumbs-down on whether the phase 3 trial provides “strong evidence that supports the effectiveness” of the drug as a treatment for Alzheimer’s. Two abstained. A second vote on whether a small phase 1B study showed “supportive evidence” for efficacy was almost as dismal with a 7-1 no and four member abstaining.

RELATED: FDA panel slams Biogen's controversial Alzheimer's med

However, the drug came into the panel with positive FDA briefing docs. So positive, in fact, that many of the Advisory Committee members rebuked FDA officials for apparently teeing up aducanumab for a rubberstamp approval.

The committee's rejection, and additional disdain, came after consideration of two phase 3 studies, dubbed EMERGE (aka Study 301) and ENGAGE, that tested aducanumab in patients with early-stage and mild Alzheimer’s, as well as a phase 1b study where discrepancies surfaced—and continue to muddy the results.

Patients in the EMERGE trial who got the highest dose of aducanumab, for example, had a statistically significant improvement on a clinical dementia scale, but the same patient group in the ENGAGE study did worse than placebo patients on that same measure, as well as on a test of cognitive function.

Then the phase 3 program flunked a futility analysis in March 2019, which initially prompted Biogen to pull the plug on the entire program.

But in a surprise about-face eight months later, the company insisted that analysis was “incorrect.” Biogen argued it was based on a smaller data set with fewer patients who received high-dose aducanumab. By its estimation, additional data did show that aducanumab reduced clinical decline, so it decided to file for approval.

And that’s why aducanumab is still on this most-anticipated drug launch list. With Biogen executives leading the way, many still see the drug’s path clear for approval.

RELATED: FDA reputation takes another hit after scathing aducanumab advisory panel meeting

At the J.P. Morgan Healthcare conference last month, Biogen executives told aducanumab-focused investors that they were surprised by the AdComm rejection and pointed out that the committee vote is non-binding.

“There is plenty of precedence for FDA to not go along with the vote of the committee. Listen, we remain in review, and we’ll find out hopefully by March 7 what their decision is,” Al Sandrock, head of Biogen’s R&D, said.

That precedence includes a pair of Duchenne muscular dystrophy drugs from Sarepta Therapeutics. Exondys 51 got a nod in 2016 despite limited data and a negative advisory panel recommendation, and more recently, its Vyondys 53, initially rejected by the FDA in August 2019, got a surprise green light in December that year. It’s worth noting the aducanumab approval went through the same FDA neuroscience group, led by director Billy Dunn, as the Sarepta drugs.

Now, though, Biogen—and the rest of the world—will have to wait even longer for a decision. Originally set for a final yea or nay in March, the FDA last month pushed its decision back another three months to early June. Biogen shares leapt on the news as some market watchers saw the delay as a sign the FDA is truly considering an approval despite the AdComm's down vote.

If it's approved, Evaluate estimates track a modest 2021 start at $271 million in sales and $765 million for 2022, but then sees the drug taking off and reaching $4.94 billion by 2026.

1. Aducanumab