Post by icemandios on Jan 5, 2023 14:27:56 GMT
January 3, 2023 08:23 AM ESTUpdated 09:34 AM PharmaFDA+
Congressional inquiry into 'highly atypical' FDA-Biogen ties ends with damning report, no repercussions
Zachary Brennan
Senior Editor
The FDA’s controversial approval of Biogen’s amyloid-targeted Alzheimer’s drug Aduhelm was “highly atypical” and “deviated” from FDA’s standard practices “in significant respects,” two key congressional committees late last week said in a report following an 18-month investigation into what transpired.
While the cozy ties that contributed to the approval, as revealed in this new report, may look like a slap in the face for both Biogen and FDA, at the end of the day the report offers a roadmap for how other companies may leverage behind-the-scenes interactions with FDA leaders to their advantage, and neither Biogen nor the FDA will face any consequences for their actions, at least as part of this investigation. The SEC, FTC and HHS’ OIG inquiries are still probing what happened.
The final congressional report, based on multiple briefings with FDA and congressional staff who reviewed more than 500,000 pages of documents from FDA and Biogen, reveals an uncharacteristically close relationship between the head of FDA’s neuroscience division, Billy Dunn, and senior executives at Biogen, that was never documented, with FDA noting in its own internal review of the situation that there isn’t even a “clear record of the number and nature of interactions between the sponsor and FDA.”
Samantha Budd Haeberlein
Whereas pharma companies frequently complain about not enough engagement with the FDA during any given drug’s approval process, this investigation found FDA and Biogen engaged at every level, across at least 115 meetings, calls and email exchanges concerning Aduhelm’s application, and featuring “at least 45 collaborative workstream meetings” that Dunn and Samantha Budd Haeberlein, Biogen’s head of clinical development, attended and that were outside the normal stream of FDA-sponsor meetings.
FDA reviewers and the agency’s report noted that these regular meetings between Biogen and the agency were “not typical of other development programs,” but FDA ultimately legitimized the decision by concluding that the interactions “were consistent with the agency’s public health mission given the potential for the first disease modifying drug for Alzheimer’s disease.”
Whether Aduhelm is actually the first disease-modifying Alzheimer’s drug remains an open question, and one that led CMS to only cover the drug (and all other subsequent amyloid-targeted Alzheimer’s drugs) under additional randomized trials, leading to dismal sales so far.
Aduhelm — which may have peaked on the day of its approval with its $18 billion peak annual projection — has fallen to the point that Biogen said earlier this summer in an SEC filing that its $230 million stash of Aduhelm should be considered worthless.
For accounting purposes, Biogen says its $223M inventory of Aduhelm is basically worthless
Statistical reviewers at FDA were clearly at odds with Dunn and the company’s interpretation of the results for the studies that proved pivotal to Aduhelm’s approval.
“The scientific dispute between the Office of Neuroscience and the statistics team in the Division of Biometrics I was not addressed early enough in the process, making it difficult to engage up the management chain in advance of the Advisory Committee meeting,” the FDA acknowledged in its internal review, according to documents released by the committee.
And ahead of the unanimously negative adcomm for Aduhelm, which FDA and Biogen worked on the briefing documents collaboratively, the FDA now acknowledges that given the internal disagreement between its neurology and biostats divisions, “and the lack of a unified FDA perspective on the data, the use of the joint briefing document was not an appropriate approach in this instance.”
On the pricing end — Biogen famously priced Aduhelm at $56,000 per year and then sliced that in half after significant pushback — the report reveals a company ready to turn Aduhelm into the biggest blockbuster of all time, even if it’ll take up more than one-third of Medicare’s annual budget, and even as consultants commissioned by Biogen suggested that a price higher than $40,000 per year would maximize revenue, but faced backlash.
The Boston-based company, working off the claim that Aduhelm delays moderate Alzheimer’s by 2.6 years, was ready to pump more than $3.3 billion into sales and marketing of the drug from 2020 to 2024, which according to the congressional report, amounts to more than two and a half times what Biogen spent in total R&D on the drug dating back to 2007.
An Endpoints News investigation last year into Biogen sales practices also revealed the company was planning to ramp up sales of the drug even after CMS indicated it likely wouldn’t cover it.
But as far as recommendations moving forward to ensure that other companies don’t attempt similar behind-the-scenes moves with the normally impartial regulator, both the congressional committees and the FDA offered lukewarm ideas for changes.
For instance, the FDA internal report said this application “should have had more visibility at the OND and CDER leadership level” and that as far as the “frequent interactions” between FDA and Biogen around joint analyses of the data on an ongoing basis, the FDA said “it maybe advisable to either have the Type C meeting minutes generally describe the number and nature of the interactions since the last Type C meeting or maintain informal notes, even if just a bulleted email summary.”
The congressional committees, meanwhile, called on the FDA “to ensure that all substantive interactions with sponsors are documented,” establish clearer rules around when joint briefing documents for adcomms are necessary, and “take swift action to ensure that its processes for reviewing future Alzheimer’s disease treatments do not lead to the same doubts about the integrity of FDA’s review.”
Biogen and Eisai’s next Alzheimer’s drug lecanemab is likely to win accelerated approval this week, but it remains unclear how much this controversy over Aduhelm will impact the FDA’s approval decision, confirmatory trial requirements (a full approval is expected later this year), and CMS’ likelihood to allow for coverage for another amyloid-targeted Alzheimer’s drug.
Biogen said in a statement that it “stands by the integrity of the actions we have taken.”
Congressional inquiry into 'highly atypical' FDA-Biogen ties ends with damning report, no repercussions
Zachary Brennan
Senior Editor
The FDA’s controversial approval of Biogen’s amyloid-targeted Alzheimer’s drug Aduhelm was “highly atypical” and “deviated” from FDA’s standard practices “in significant respects,” two key congressional committees late last week said in a report following an 18-month investigation into what transpired.
While the cozy ties that contributed to the approval, as revealed in this new report, may look like a slap in the face for both Biogen and FDA, at the end of the day the report offers a roadmap for how other companies may leverage behind-the-scenes interactions with FDA leaders to their advantage, and neither Biogen nor the FDA will face any consequences for their actions, at least as part of this investigation. The SEC, FTC and HHS’ OIG inquiries are still probing what happened.
The final congressional report, based on multiple briefings with FDA and congressional staff who reviewed more than 500,000 pages of documents from FDA and Biogen, reveals an uncharacteristically close relationship between the head of FDA’s neuroscience division, Billy Dunn, and senior executives at Biogen, that was never documented, with FDA noting in its own internal review of the situation that there isn’t even a “clear record of the number and nature of interactions between the sponsor and FDA.”
Samantha Budd Haeberlein
Whereas pharma companies frequently complain about not enough engagement with the FDA during any given drug’s approval process, this investigation found FDA and Biogen engaged at every level, across at least 115 meetings, calls and email exchanges concerning Aduhelm’s application, and featuring “at least 45 collaborative workstream meetings” that Dunn and Samantha Budd Haeberlein, Biogen’s head of clinical development, attended and that were outside the normal stream of FDA-sponsor meetings.
FDA reviewers and the agency’s report noted that these regular meetings between Biogen and the agency were “not typical of other development programs,” but FDA ultimately legitimized the decision by concluding that the interactions “were consistent with the agency’s public health mission given the potential for the first disease modifying drug for Alzheimer’s disease.”
Whether Aduhelm is actually the first disease-modifying Alzheimer’s drug remains an open question, and one that led CMS to only cover the drug (and all other subsequent amyloid-targeted Alzheimer’s drugs) under additional randomized trials, leading to dismal sales so far.
Aduhelm — which may have peaked on the day of its approval with its $18 billion peak annual projection — has fallen to the point that Biogen said earlier this summer in an SEC filing that its $230 million stash of Aduhelm should be considered worthless.
For accounting purposes, Biogen says its $223M inventory of Aduhelm is basically worthless
Statistical reviewers at FDA were clearly at odds with Dunn and the company’s interpretation of the results for the studies that proved pivotal to Aduhelm’s approval.
“The scientific dispute between the Office of Neuroscience and the statistics team in the Division of Biometrics I was not addressed early enough in the process, making it difficult to engage up the management chain in advance of the Advisory Committee meeting,” the FDA acknowledged in its internal review, according to documents released by the committee.
And ahead of the unanimously negative adcomm for Aduhelm, which FDA and Biogen worked on the briefing documents collaboratively, the FDA now acknowledges that given the internal disagreement between its neurology and biostats divisions, “and the lack of a unified FDA perspective on the data, the use of the joint briefing document was not an appropriate approach in this instance.”
On the pricing end — Biogen famously priced Aduhelm at $56,000 per year and then sliced that in half after significant pushback — the report reveals a company ready to turn Aduhelm into the biggest blockbuster of all time, even if it’ll take up more than one-third of Medicare’s annual budget, and even as consultants commissioned by Biogen suggested that a price higher than $40,000 per year would maximize revenue, but faced backlash.
The Boston-based company, working off the claim that Aduhelm delays moderate Alzheimer’s by 2.6 years, was ready to pump more than $3.3 billion into sales and marketing of the drug from 2020 to 2024, which according to the congressional report, amounts to more than two and a half times what Biogen spent in total R&D on the drug dating back to 2007.
An Endpoints News investigation last year into Biogen sales practices also revealed the company was planning to ramp up sales of the drug even after CMS indicated it likely wouldn’t cover it.
But as far as recommendations moving forward to ensure that other companies don’t attempt similar behind-the-scenes moves with the normally impartial regulator, both the congressional committees and the FDA offered lukewarm ideas for changes.
For instance, the FDA internal report said this application “should have had more visibility at the OND and CDER leadership level” and that as far as the “frequent interactions” between FDA and Biogen around joint analyses of the data on an ongoing basis, the FDA said “it maybe advisable to either have the Type C meeting minutes generally describe the number and nature of the interactions since the last Type C meeting or maintain informal notes, even if just a bulleted email summary.”
The congressional committees, meanwhile, called on the FDA “to ensure that all substantive interactions with sponsors are documented,” establish clearer rules around when joint briefing documents for adcomms are necessary, and “take swift action to ensure that its processes for reviewing future Alzheimer’s disease treatments do not lead to the same doubts about the integrity of FDA’s review.”
Biogen and Eisai’s next Alzheimer’s drug lecanemab is likely to win accelerated approval this week, but it remains unclear how much this controversy over Aduhelm will impact the FDA’s approval decision, confirmatory trial requirements (a full approval is expected later this year), and CMS’ likelihood to allow for coverage for another amyloid-targeted Alzheimer’s drug.
Biogen said in a statement that it “stands by the integrity of the actions we have taken.”