Getting Approved is Nice; Getting Paid is Something Else
Jun 10, 2021 17:50:32 GMT
c2crusher likes this
Post by icemandios on Jun 10, 2021 17:50:32 GMT
UPDATE: Will Biogen ever publish the trial results for its new Alzheimer’s drug?
Zachary Brennan
Senior Editor
Usually when a new drug is approved by the FDA, physicians who might use that drug can turn to the medical literature for a deeper understanding of who exactly might benefit from it, what exactly occurred in the clinical trials (beyond the company’s press release), and why the agency signed off on it.
But in the case of Biogen’s new controversial Alzheimer’s drug Aduhelm (aducanumab), it’s unclear if the company will go the extra mile and try to publish the data, particularly as the only positive data was from a post-hoc analysis of one of the two trials that failed.
Those data are important as some experts are now raising questions about what the FDA released alongside the approval, and as two of the adcomm members have now resigned from the panel.
Scott Emerson
Scott Emerson, professor emeritus of biostatistics at the University of Washington and a member of the FDA adcomm that voted against Aduhelm, told Endpoints News via email that he did not think the accelerated approval pathway was appropriate for the drug, calling it “particularly ill-advised and disappointing.”
He also noted that the package insert for the new drug fails to explain that the high-dose group in one of the two trials did worse than placebo, and worse than the low-dose group.
“The package insert seems written to facilitate the Sponsor making misleading claims about evidence of clinical efficacy,” Emerson said.
“This is made all the worse by the fact that the sponsor has yet to publish the results of these two clinical trials in a peer reviewed medical journal. Thus clinicians do not have their regular sources for judging the validity of sponsor claims about the drug,” Emerson added, noting that he suspects Biogen “is reluctant to have the full data undergo the greater scrutiny that the peer review process would provide” and the FDA clinical review “certainly did not provide all the information that I would have wanted.”
Peter Bach
But others like Peter Bach, Director of Memorial Sloan Kettering’s Center for Health Policy and Outcomes, told Endpoints he thought Biogen could find somewhere to publish its results, but he doesn’t think they will try because it could make them more vulnerable.
“I tell my trainees, ‘There is always a journal for every paper,’” Bach said. “A positive trial would lead to very rapid uptake and massive revenues and their current path will be an uncertain slog by contrast. Likewise, companies that believe in their data do ‘all-hands’ to get papers written quickly and submitted, and a good paper with believable data on this drug – negative or positive – is a shoo in for a top flight journal,” Bach noted. “But if the reality is that publishing just makes them more vulnerable (just like doing another trial which they know would be negative), they just won’t do it.
“It’s sort of like how you aren’t supposed to post selfies on Instagram as you are robbing the Brinks truck,” he added.
Walid Gellad
Walid Gellad, director of the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing, also told Endpoints that he did not think “a trial stopped for futility and manipulated in this way would get published – nope.” But he also said that he thinks all the data are in the FDA report and that he knows of people at insurers who are downloading it and getting ready to dig in, “so payers have all data they need.”
Biogen did not respond to a request for comment on whether the results would be published. The FDA said in an emailed statement, “FDA Oncology has often approved products in advance of the pivotal trial publication. One recent example was [Amgen’s Lumakras] sotorasib.” Lumakras’ approval was based on the results from a Phase II trial published last Friday in the New England Journal of Medicine, exactly one week after the approval.
Since the aducanumab approval decision on Monday, two members of that adcomm have since resigned, Joel Perlmutter, a neurologist at Washington University in St. Louis and David Knopman, a neurologist at the Mayo Clinic (although Knopman was recused from the actual meeting because he worked on one of the Biogen trials).
Knopman told the Washington Post that he did not “wish to be part of a sham process” that resulted in the agency’s approval, and Perlmutter told STAT that he quit on Monday “due to this ruling by the FDA without further discussion with our advisory committee.”
Madhav Thambisetty
Others who were on it, like Emerson, said they want to remain on it so their dissenting views can continue to be heard.
Madhav Thambisetty, senior investigator at the NIH’s National Institute on Aging and a member of the aducanumab adcomm, told Endpoints that his plan to stay on the adcomm has not changed.
“Regarding the approval decision, the FDA Advisory committee was clear in its consensus that the data presented did not show a clear signal of efficacy with aducanumab. Gathering post-marketing data in a timely manner and publishing them rapidly will be in the best interests of our patients as it will empower them to make informed risk-versus-benefit decisions about their care,” Thambisetty said.
Editor’s note: Article updated with comment from FDA and more detail on the adcomm member resignations.
Zachary Brennan
Senior Editor
Usually when a new drug is approved by the FDA, physicians who might use that drug can turn to the medical literature for a deeper understanding of who exactly might benefit from it, what exactly occurred in the clinical trials (beyond the company’s press release), and why the agency signed off on it.
But in the case of Biogen’s new controversial Alzheimer’s drug Aduhelm (aducanumab), it’s unclear if the company will go the extra mile and try to publish the data, particularly as the only positive data was from a post-hoc analysis of one of the two trials that failed.
Those data are important as some experts are now raising questions about what the FDA released alongside the approval, and as two of the adcomm members have now resigned from the panel.
Scott Emerson
Scott Emerson, professor emeritus of biostatistics at the University of Washington and a member of the FDA adcomm that voted against Aduhelm, told Endpoints News via email that he did not think the accelerated approval pathway was appropriate for the drug, calling it “particularly ill-advised and disappointing.”
He also noted that the package insert for the new drug fails to explain that the high-dose group in one of the two trials did worse than placebo, and worse than the low-dose group.
“The package insert seems written to facilitate the Sponsor making misleading claims about evidence of clinical efficacy,” Emerson said.
“This is made all the worse by the fact that the sponsor has yet to publish the results of these two clinical trials in a peer reviewed medical journal. Thus clinicians do not have their regular sources for judging the validity of sponsor claims about the drug,” Emerson added, noting that he suspects Biogen “is reluctant to have the full data undergo the greater scrutiny that the peer review process would provide” and the FDA clinical review “certainly did not provide all the information that I would have wanted.”
Peter Bach
But others like Peter Bach, Director of Memorial Sloan Kettering’s Center for Health Policy and Outcomes, told Endpoints he thought Biogen could find somewhere to publish its results, but he doesn’t think they will try because it could make them more vulnerable.
“I tell my trainees, ‘There is always a journal for every paper,’” Bach said. “A positive trial would lead to very rapid uptake and massive revenues and their current path will be an uncertain slog by contrast. Likewise, companies that believe in their data do ‘all-hands’ to get papers written quickly and submitted, and a good paper with believable data on this drug – negative or positive – is a shoo in for a top flight journal,” Bach noted. “But if the reality is that publishing just makes them more vulnerable (just like doing another trial which they know would be negative), they just won’t do it.
“It’s sort of like how you aren’t supposed to post selfies on Instagram as you are robbing the Brinks truck,” he added.
Walid Gellad
Walid Gellad, director of the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing, also told Endpoints that he did not think “a trial stopped for futility and manipulated in this way would get published – nope.” But he also said that he thinks all the data are in the FDA report and that he knows of people at insurers who are downloading it and getting ready to dig in, “so payers have all data they need.”
Biogen did not respond to a request for comment on whether the results would be published. The FDA said in an emailed statement, “FDA Oncology has often approved products in advance of the pivotal trial publication. One recent example was [Amgen’s Lumakras] sotorasib.” Lumakras’ approval was based on the results from a Phase II trial published last Friday in the New England Journal of Medicine, exactly one week after the approval.
Since the aducanumab approval decision on Monday, two members of that adcomm have since resigned, Joel Perlmutter, a neurologist at Washington University in St. Louis and David Knopman, a neurologist at the Mayo Clinic (although Knopman was recused from the actual meeting because he worked on one of the Biogen trials).
Knopman told the Washington Post that he did not “wish to be part of a sham process” that resulted in the agency’s approval, and Perlmutter told STAT that he quit on Monday “due to this ruling by the FDA without further discussion with our advisory committee.”
Madhav Thambisetty
Others who were on it, like Emerson, said they want to remain on it so their dissenting views can continue to be heard.
Madhav Thambisetty, senior investigator at the NIH’s National Institute on Aging and a member of the aducanumab adcomm, told Endpoints that his plan to stay on the adcomm has not changed.
“Regarding the approval decision, the FDA Advisory committee was clear in its consensus that the data presented did not show a clear signal of efficacy with aducanumab. Gathering post-marketing data in a timely manner and publishing them rapidly will be in the best interests of our patients as it will empower them to make informed risk-versus-benefit decisions about their care,” Thambisetty said.
Editor’s note: Article updated with comment from FDA and more detail on the adcomm member resignations.