|
 The FDA has granted so-called "accelerated approval" in more than
250 instances since 1992, mainly for rare diseases or small patient
populations that have had no effective treatments available to them.
In these cases, the agency requires that drugmakers conduct
additional clinical trials to prove their therapy works, or face
withdrawal from the market. Aduhelm, however, is in a different
league in terms of the number of potential patients and cost to the
healthcare system.
In addition, the FDA approval ignored the recommendation of its
outside advisors, who said Biogen did not provide enough evidence of
clinical benefit. Three of the advisory panel's members have
resigned in protest since the FDA decision was announced on Monday.
"This decision has shaken the foundations of the scientific process
and methods," said Dr. Jason Karlawish, co-director of the Penn
Memory Center in Philadelphia. Karlawish ran one of the trial sites
for the Biogen drug.
He said the FDA made its decision "by fiat," and had not asked its
advisors to consider whether the drug's ability to remove a type of
brain plaques known as beta amyloid would improve outcomes for
patients. "It's a disturbing set of events, scientifically,
clinically, politically," Karlawish said. Biogen has said that some
1.5 million Americans with early-stage Alzheimer's will be eligible
for the drug, priced at an average of $56,000 per year, with the
federal Medicare insurance program for seniors likely on the hook
for most of the cost.
The FDA approval allows Biogen to sell its product over several
years - with forecasts for potential annual sales reaching as high
$10 billion to $50 billion - until the company completes a required
follow-up study. "No amount of unmet need can take the place of
sufficient evidence," said Johns Hopkins public health professor Dr.
Caleb Alexander, a member of the FDA advisory panel.
The number of Americans living with Alzheimer's is expected to more
than double to around 13 million by 2050, according to the
Alzheimer's Association.
Biogen research chief Alfred Sandrock said the FDA had painstakingly
analyzed its clinical trial data over two years before reaching a
conclusion.
"I believe they came to the right decision on behalf of the American
public," Sandrock said in an interview.
A VIEW FROM THE FDA The FDA has defended its decision by saying that
Biogen presented clear evidence that Aduhelm, known chemically as
aducanumab, removed beta amyloid from the brains of people with
Alzheimer’s.
Amyloid has long been a target of experimental therapies for the
disease. However, none of the earlier drugs have shown that
reductions in amyloid resulted in significant benefits for patients
by slowing deteriorating cognition or ability to function.
[to top of second column] |
 Dr. Peter Stein, director of
the FDA's Office of New Drugs, told Reuters that
Aduhelm showed the clearest correlation so far
between a reduction in beta amyloid and a delay
in cognitive decline among patients, suggesting
it was a good predictor of clinical benefit. FDA
officials said other Alzheimer's drug developers
cannot assume their therapies will be considered
under the same framework. Eli Lilly and Co and
Roche Holding AG are among drugmakers also
working on amyloid-targeting medicines.
"We can't say right now whether this will be a
path for other Alzheimer's drugs, or drugs for
other neurodegenerative diseases," Dr. Patrizia
Cavazzoni, director of the FDA's Center for Drug
Evaluation and Research, told Reuters.
Critics are less convinced that amyloid removal
is an adequate proxy to predict benefit. "We
need to rethink the use of these regulations as
interpreted and used by FDA," said Karlawish.
Nearly half of all drugs receiving accelerated
approval ultimately got full approval, after a
median of around three years, according to a
report by the Institute for Clinical and
Economic Review (ICER), a drug cost watchdog.
Exceptions include Lilly's Lartruvo for sarcoma,
which was withdrawn, while the FDA revoked its
authorization for Roche's Avastin to treat
breast cancer, although it is still used for
other cancers.
More than 100 drugs with accelerated approvals
have been on the market a median of just under
two years, according to ICER. The report noted
that many of the confirmatory trials are slow to
complete, and the results often ambiguous.
 "The agency has gotten comfortable with the
accelerated approval pathway," said attorney Jim
Shehan, head of FDA regulatory practice at law
firm Lowenstein Sandler. Biogen has said a
confirmatory Aduhelm trial could take nine years
to complete. The FDA described that estimate as
“conservative” and said it would support
“efforts to complete this trial in the shortest
possible timeline.” Despite Aduhelm's high
price, patient advocates hailed the FDA
decision, saying it will revive research in the
field, including the kinds of drug combinations
that have improved treatment of complex diseases
like cancer and HIV. "This approval will spark
additional investment by other companies in
disease-modifying treatments and therapies,"
advocacy group UsAgainstAlzheimer's said in a
statement.
(Reporting by Deena Beasley in Los Angeles and
Julie Steenhuysen in Chiacgo; Editing by Michele
Gershberg 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 |
