Post by icemandios on Jun 10, 2021 15:56:15 GMT
June 10, 2021 11:03 AM EDTUpdated 11:14 AM PharmaFDA+
A second adcomm member abandons his post in aftermath of controversial aducanumab decision
Nicole DeFeudis
Associate Editor
Max Gelman
Associate Editor
As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?
The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.
Knopman, who was serving a term from 2018 to 2022, told Endpoints News that he “didn’t wish to be in the position, in the future, that the aducanumab advisory committee members were put in over the past 8 months.” He declined to comment any further.
The scientist shared a copy of his resignation letter with the Washington Post, in which he told FDA officials: “The whole saga of the approval of aducanumab … made a mockery of the [advisory] committee’s consultative process. While I realize that the committee is advisory, the approval of aducanumab appears [to] have been foreordained.”
Knopman didn’t actually vote during aducanumab’s advisory committee meeting back in November, as he was recused because he worked on one of the Biogen trials. But the decision was nearly unanimous: When asked whether it is reasonable to consider the positive Phase III Biogen submitted “as primary evidence of effectiveness” for the treatment of Alzheimer’s disease, 10 voted no, none said yes and one abstained.
Though the FDA is not required to follow all of its advisory panel recommendations, it does so more often than not. According to an outside study examining 376 adcomm votes and corresponding decisions between 2008 and 2015, US regulators break from their advisers about 22% of the time.
When the agency chose to go against the panels, however, they typically implemented restrictive measures to limit the use of drugs with tenuous data. These instances occurred in about 3 of every 4 cases, the study authors wrote.
It was widely expected that if an approval came for Aduhelm, it would be for the earliest stage patients. Instead, the FDA approved it for all Alzheimer’s patients based on evidence that the drug had an impact on clearing a sticky protein called amyloid, which CDER director Patrizia Cavazzoni says is “reasonably likely” to mean the drug will slow patients’ mental decline.
“Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible,” Knopman said in his resignation letter, via The Post.
Joel Perlmutter
Knopman’s resignation comes after Joel Perlmutter, a neurologist from Washington University in St. Louis, reportedly quit the panel earlier this week. Perlmutter confirmed his exit in an email to Endpoints, saying he left in protest of the FDA’s decision to approve Aduhelm.
Chief among Perlmutter’s concerns centered around Biogen’s use of the amyloid beta plaque as a surrogate endpoint, reasserting that there isn’t enough evidence to predict whether removing the plaque can result in a clinical benefit. Coupled with the brain lesions observed in Biogen’s trials, which Aduhelm causes “frequently,” Perlmutter said this all amounts to a “major problem” with the FDA’s decision.
He listed several other reasons for his decision to quit, including the impact on future Alzheimer’s studies and the cost associated with Biogen’s drug. Elaborating, Perlmutter wrote:
Approval of a drug that is not effective has serious potential to impair future research into new treatments that may be effective for treating AD. For example, new AD studies may be required to no longer compare an investigational drug to placebo — as would be the standard — but rather may have to compare to aducanumab. Enthusiasm (from either potential volunteer participants or funders) for new treatments may wane due to thinking that we already have an effective treatment, when in fact we do not. These are potentially very serious issues for helping all of these people and families affected by AD. In addition, the implementation of aducanumab therapy will potentially cost billions of dollars, and these dollars may be better spent in either developing stronger evidence for aducanumab or other therapeutic interventions.”
Both Perlmutter and Knopman were due to leave the committee in 2022. Perlmutter’s term was originally supposed to end in 2020, but was extended two years.
Scott Emerson
It remains to be seen whether these resignations will continue or not. Scott Emerson had previously told Endpoints that while he disagreed with the approval, particularly with the use of the accelerated pathway, he wants to remain on the panel to ensure dissenting voices will continue to be heard. Endpoints has reached out to other adcomm members and will continue updating accordingly.
Madhav Thambisetty also said he’s planning on staying, citing the need to continue reviewing Aduhelm’s post-marketing data. And Thambisetty spoke out against the decision on Thursday, aiming to clear up “misconceptions” over whether the panel discussed accelerated approval.
To correct misperceptions on whether the Adcom discussed "accelerated approval" #Aducanumab #FDA statement clearly states:
"The option of Accelerated Approval was not discussed by the Advisory Committee".
The full statement is at:
t.co/eF8EDYIwa0
— Madhav Thambisetty (@madhavthambiset) June 10, 2021
A second adcomm member abandons his post in aftermath of controversial aducanumab decision
Nicole DeFeudis
Associate Editor
Max Gelman
Associate Editor
As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?
The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.
Knopman, who was serving a term from 2018 to 2022, told Endpoints News that he “didn’t wish to be in the position, in the future, that the aducanumab advisory committee members were put in over the past 8 months.” He declined to comment any further.
The scientist shared a copy of his resignation letter with the Washington Post, in which he told FDA officials: “The whole saga of the approval of aducanumab … made a mockery of the [advisory] committee’s consultative process. While I realize that the committee is advisory, the approval of aducanumab appears [to] have been foreordained.”
Knopman didn’t actually vote during aducanumab’s advisory committee meeting back in November, as he was recused because he worked on one of the Biogen trials. But the decision was nearly unanimous: When asked whether it is reasonable to consider the positive Phase III Biogen submitted “as primary evidence of effectiveness” for the treatment of Alzheimer’s disease, 10 voted no, none said yes and one abstained.
Though the FDA is not required to follow all of its advisory panel recommendations, it does so more often than not. According to an outside study examining 376 adcomm votes and corresponding decisions between 2008 and 2015, US regulators break from their advisers about 22% of the time.
When the agency chose to go against the panels, however, they typically implemented restrictive measures to limit the use of drugs with tenuous data. These instances occurred in about 3 of every 4 cases, the study authors wrote.
It was widely expected that if an approval came for Aduhelm, it would be for the earliest stage patients. Instead, the FDA approved it for all Alzheimer’s patients based on evidence that the drug had an impact on clearing a sticky protein called amyloid, which CDER director Patrizia Cavazzoni says is “reasonably likely” to mean the drug will slow patients’ mental decline.
“Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible,” Knopman said in his resignation letter, via The Post.
Joel Perlmutter
Knopman’s resignation comes after Joel Perlmutter, a neurologist from Washington University in St. Louis, reportedly quit the panel earlier this week. Perlmutter confirmed his exit in an email to Endpoints, saying he left in protest of the FDA’s decision to approve Aduhelm.
Chief among Perlmutter’s concerns centered around Biogen’s use of the amyloid beta plaque as a surrogate endpoint, reasserting that there isn’t enough evidence to predict whether removing the plaque can result in a clinical benefit. Coupled with the brain lesions observed in Biogen’s trials, which Aduhelm causes “frequently,” Perlmutter said this all amounts to a “major problem” with the FDA’s decision.
He listed several other reasons for his decision to quit, including the impact on future Alzheimer’s studies and the cost associated with Biogen’s drug. Elaborating, Perlmutter wrote:
Approval of a drug that is not effective has serious potential to impair future research into new treatments that may be effective for treating AD. For example, new AD studies may be required to no longer compare an investigational drug to placebo — as would be the standard — but rather may have to compare to aducanumab. Enthusiasm (from either potential volunteer participants or funders) for new treatments may wane due to thinking that we already have an effective treatment, when in fact we do not. These are potentially very serious issues for helping all of these people and families affected by AD. In addition, the implementation of aducanumab therapy will potentially cost billions of dollars, and these dollars may be better spent in either developing stronger evidence for aducanumab or other therapeutic interventions.”
Both Perlmutter and Knopman were due to leave the committee in 2022. Perlmutter’s term was originally supposed to end in 2020, but was extended two years.
Scott Emerson
It remains to be seen whether these resignations will continue or not. Scott Emerson had previously told Endpoints that while he disagreed with the approval, particularly with the use of the accelerated pathway, he wants to remain on the panel to ensure dissenting voices will continue to be heard. Endpoints has reached out to other adcomm members and will continue updating accordingly.
Madhav Thambisetty also said he’s planning on staying, citing the need to continue reviewing Aduhelm’s post-marketing data. And Thambisetty spoke out against the decision on Thursday, aiming to clear up “misconceptions” over whether the panel discussed accelerated approval.
To correct misperceptions on whether the Adcom discussed "accelerated approval" #Aducanumab #FDA statement clearly states:
"The option of Accelerated Approval was not discussed by the Advisory Committee".
The full statement is at:
t.co/eF8EDYIwa0
— Madhav Thambisetty (@madhavthambiset) June 10, 2021