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 The Biogen Inc drug, Aduhelm, was authorized based on evidence that
it can reduce brain plaques, a likely contributor to Alzheimer's,
rather than proof that it slows progression of the lethal
mind-wasting disease.
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.
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 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.
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)
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