|
 The memos reveal disagreements within the agency, with some
departments in support of traditional approval and others arguing
against.
Ultimately, after months of internal deliberations, agency officials
approved the drug using its accelerated approval pathway, which
requires a study to confirm the that the drug works as intended.
The June 7 approval has been met with fierce opposition by some
scientists criticizing the FDA's decision making, culminating in the
public resignations of three of the 11 members of its independent
advisory panel.
One of those members, Dr. Aaron Kesselheim of Harvard-affiliated
Brigham and Women's Hospital, wrote in his resignation letter that
it was the "worst drug approval decision in recent U.S. history."
The drug was approved in spite of the fact that one of its two
large-scale clinical trials failed to show a benefit to patients.
The FDA's Office of Biostatistics in particular concluded that
"substantial evidence of effectiveness had not been provided in the
application," citing "inconsistencies in the data" that led the
group to not support approval. That full document has not been
released.
In an interview with Reuters, FDA officials said they considered the
advisory panel's recommendation against approval as a "reset point"
in their thinking, prompting them to consider the accelerated
approval pathway after concluding that the drug had not met the high
standard for regular approval.
"What we heard really shaped our thinking in our discussions over
these almost seven months between the advisory committee and the
approval," said Dr. Patrizia Cavazzoni, director of the FDA's Center
for Drug Evaluation and Research.
Instead of direct evidence of a clinical benefit from the trials,
the FDA's accelerated approval pathway relies on the use of a
biomarker - a biological change prompted by the drug - that could
likely predict a patient benefit.
Dr. Peter Stein, director of FDA's Office of New Drugs, agreed that
the medicine had not met the standard for full approval, but said it
did meet FDA's standard for accelerated approval, which is typically
used for drugs for diseases with no other effective treatments.
Stein said Biogen's data showed a relationship between removing the
protein beta amyloid from patients' brains, believed to be
contributor to Alzheimer's disease, and improvements seen in its
clinical trials.
Cavazzoni said the agency's review of the data showed that amyloid
reduction tracks "quite convincingly" with improvements in slowing
the progression of Alzheimer's.
[to top of second column] |
 The early release of some of
its decision memos - which usually follow a
month to six weeks after an agency approval -
was part of an effort to disclose the FDA's
decisionmaking process, she said.
"We were really quite struck that the data were compelling, and it
behooved us to continue to really discuss and review these data and
understand it to the fullest," Cavazzoni said.
'STILL BEING WORKED OUT'
Experts, however, have argued that several drugs in prior
Alzheimer's trials have removed amyloid but failed to impact disease
progression.
Dr. Paul Aisen, director of the University of Southern California's
Alzheimer's Therapy Research Institute in San Diego, and a paid
adviser to Biogen, said he believes Aduhelm benefits patients, but
disagrees that removing amyloid has been shown to correlate with
patient benefits. "One of the risks is it suggests
that any drug that lowers amyloid in any population with Alzheimer's
disease is justified," Aisen said after reviewing the FDA documents.
"We have not established that."
Dr. Jason Karlawish, co-director of the Penn Memory Center in
Philadelphia who ran one of the trial sites for the Biogen drug,
said the documents reveal clear disagreement.
"The science around this particular relationship between amyloid and
clinical response is still being worked out," he said. The agency
should have reconvened its advisory board to weigh in on the matter,
he said.
Some six million people in the United States are living with
Alzheimer's disease, although Aduhelm is likely to be used only on
those in its early stages - the type of patients who took part in
Biogen's trials.
Biogen has stated publicly that it could take nine years to complete
a study confirming whether removing amyloid really slows the ravages
of the fatal mind-wasting disease.
Stein said the agency is already in talks with the company about
designing that trial.
"I'm very hopeful that the answer will come years before that
nine-year period," he said.
(Reporting by Julie Steenhuysen in Chicago; Editing by Peter
Henderson, Lisa Shumaker and Bill Berkrot)
[© 2021 Thomson Reuters. All rights
reserved.] Copyright 2021 Reuters. All rights reserved. This material may not be published,
broadcast, rewritten or redistributed.
Thompson Reuters is solely responsible for this content |
