Mayo Clinic neurologist David Knopman, M.D., has been kicked off an advisory committee assessing Biogen’s controversial Alzheimer’s disease hopeful aducanumab that's meeting later this week.
Knopman will now not help review the drug via the FDA advisory committee on Friday, with the regulator citing “conflicts of interest,” for his removal, according to Reuters.
Knopman was one of a 11-strong team set to review the drug, which has failed major trials in the past. But Biogen, digging deep, thought it saw some glimmers of efficacy and is pressing forward for an FDA approval.
Knopman had, in fact, been involved in some of these trials, hence the formal requirement for his recusal, though he has also been a major critic of the drug, which at one point was very nearly shelved until Biogen starting its data mining process.
The data underpinning the filing come from two phase 3 studies dubbed EMERGE and ENGAGE that tested aducanumab in patients with early-stage and mild Alzheimer’s, as well as from a phase 1b study.
There was a discrepancy between the phase 3 studies—patients in the EMERGE trial who got the highest dose of aducanumab had a statistically significant improvement on a clinical dementia scale, but the same patient group in the ENGAGE study did worse than patients taking placebo on that same measure, as well as on a test of cognitive function.
What's more, the phase 3 program flunked a futility analysis in March 2019, leading Biogen to pull the plug on the studies, but the company about-faced eight months later, saying the analysis was “incorrect.”
Biogen argued the futility analysis was based on a smaller data set that featured fewer patients who received high-dose aducanumab. Adding in the additional data showed aducanumab reduced clinical decline, the company said at the time, and then decided to file. It has little to lose in trying, and its attempt comes after several years of R&D setbacks and mounting pressure on its key franchises.
If approved next March, it would be the first new Alzheimer’s med in nearly two decades, following a growing field of R&D failures in an area that has simply not yielded new treatments good and safe enough to treat the memory-wasting disease, which is still one of the biggest causes of death in the Western world.
The FDA does not have to follow the advice of an advisory committee, but it typically does. Knopman’s recusal was seen as a small positive for the pharma, though many of the bigger biotech analysts still see Biogen’s chances of notching an approval as very low, despite the pressure and need for new drugs.
There could also be a further complication: With a U.S. election this week, a new president could decide to replace President Donald Trump's pick Stephen Hahn, M.D., with a new FDA commissioner, who could have a harder or softer philosophy on these sorts of decisions.