Two members of a U.S. Food and Drug Administration (FDA) advisory committee have resigned in the wake of the agency’s approval of aducanumab, the first new Alzheimer’s treatment since 2003.
Neurologists David Knopman, who works for the Mayo Clinic, and Joel Perlmutter, of Washington University St Louis, both stepped down from the board this week in protest.
Knopman and Perlmutter largely objected to the approval of the drug citing its rocky trial results with little evidence the drug was even effective.
The drug, which will be marketed under the name aduhelm is being sent out to patients in the next two weeks and will cost $56,000 per year of use.
Dr David Knopman (pictured) resigned from an FDA advisory committee after the agency gave a controversial approval to aducanumab after clinical trials showed limited effectiveness of the drug
The FDA’s approval of aducanumab adds a new drug to the arsenal of fighting Alzheimer’s for the first time since 2003. Many in the Alzheimer’s community support the drugs approval
‘The whole saga of the approval of aducanumab…made a mockery of the [advisory] committee’s consultative process,’ Knopman told the committee in an email obtained by the Washington Post.
‘While I realize that the committee is advisory, the approval of aducanumab appears [to] have been foreordained.’
Meanwhile, Perlmutter told STAT News that he quit ‘due to this ruling by the FDA without further discussion with our advisory committee.’
Biogen, the Cambridge, Massachusetts-based company that developed the drug, underwent two clinical trials in 2016.
Both were stopped early as they showed the drug would fail to reach its goal.
They later took the results of one of the two trials, and found updated data that the drug had slowed the cognitive decline of Alzheimer’s patients by up to 22 percent.
Many in the scientific community criticized Biogen’s claims, saying it was a post-hoc cherry-picking of data to force a conclusion.
Knopman authored a study last year, analyzing the results of Biogen’s second clinical trial, disagreeing with the claims that they showed the drug was effective.
‘We identified alternative accounts for the apparent drug benefits in post hoc subgroups that are unrelated to dose effects,’ he wrote.
‘Biomarker data were consistent with target engagement, but no evidence was presented to correlate biomarker changes to cognitive benefits.
‘Aducanumab’s efficacy as a treatment for the cognitive dysfunction in Alzheimer’s disease cannot be proven by clinical trials with divergent outcomes.
‘Based on our review of data presented publicly in December 2019, we do not agree with Biogen’s claim for efficacy of [aducanumab].’
Dr Knopman has been one of aducanumab, saying that Biogen’s trials of the drug do not show that the drug is effective in combatting Alzheimer’s
Knopman served as a site investigator for the drug, and had to recuse himself from the November advisory meeting.
While the FDA is not required the follow advice from the advisory boards, since they are made up of third parties, it is rare that members of an advisory board are more conservative on a drug than the regulatory agency.
‘I recognize that the role is advisory and yet I felt that the advisory committee in this situation was not well-treated,’ Knopman told The Post.
‘And I think that I just don’t choose to put myself into that position in the future for the FDA.’
The drug’s approval was based on its ability to reduce amyloid beta, a plaque many believes contributes to the cognitive decline in Alzheimer’s, in the brain.
Dr Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said the agency was aware of the controversy in approving the drug in a statement Monday.
‘We are well-aware of the attention surrounding this approval,’ she wrote.
‘We understand that Aduhelm has garnered the attention of the press, the Alzheimer’s patient community, our elected officials, and other interested stakeholders.’
‘With a treatment for a serious, life-threatening disease in the balance, it makes sense that so many people were following the outcome of this review.’
While some scientists and researchers oppose the drug, many in the Alzheimer’s community support its approval, as the first new treatment for the disease in 20 years could create a foothold for future research.
Aduhelm will start shipping out in two weeks to over 900 infusion centers across the country that are currently equipped to implement it.