Amgen taking different path to weight loss windfall
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[February 06, 2024]
By Deena Beasley
(Reuters) - The popularity of a new generation of weight-loss medicines
is inspiring a growing number of drugmakers to pursue paths emulating
Eli Lilly's highly-effective Zepbound, but Amgen is taking a unique
approach.
Zepbound, which promotes the most weight loss among treatment options
currently on the market, stimulates two different gut hormones to fight
obesity, GLP-1 and GIP.
Amgen's most advanced experimental candidate activates GLP-1 while
blocking GIP. It says its goal is quicker weight loss, less frequent
dosing and possibly better weight maintenance.
At stake is a slice of an obesity market some analysts forecast could
reach as much as $150 billion a year, and a significant boost to Amgen's
current revenue growth forecast.
GLP-1, which releases insulin from the pancreas and promotes feelings of
fullness, was first studied for diabetes, leading to Novo Nordisk's
successful GLP-1 drug Ozempic, which under the brand name Wegovy is the
top-selling treatment for weight loss.
Lilly's Zepbound, which is also sold as Mounjaro for type 2 diabetes, is
quickly catching up to Wegovy.
Amgen said its drug, maridebart cafraglutide, or MariTide, was developed
after genetic population data from its deCode genetics unit linked
decreased activity of the GIP receptor to lower fat mass and body
weight.
Scientists say much is still unknown about how different hormones
interact to affect appetite and metabolism.
Narimon Honarpour, Amgen's head of global clinical development, said
combining a GIP receptor blockade with GLP-1 stimulation had the
strongest impact on weight reduction compared to other strategies.
He said animal and early-stage human trial data published on Monday show
that MariTide promotes weight loss and improves metabolic markers with
an acceptable safety profile. The highest tested dose in a small Phase 1
trial led to 14.5% weight loss over 12 weeks.
Results from a mid-stage study are expected late this year.
Both Zepbound and Wegovy are given as weekly injections. Amgen's Phase 2
program is exploring several injection dosing regimens, including
monthly and less frequent shots.
Amgen has other experimental weight-loss medicines in its pipeline,
including an oral drug in Phase 1 testing.
DOUBLE-DIGIT GROWTH
Amgen shares are up more than 30% over the past year, closing at an
all-time high of $323 on Friday, compared with an 8% drop for the NYSE
Arca Biotech Index, after the company in late 2022 unveiled initial
MariTide trial results. With its current products and others in
development, including cancer and rare disease drugs, Amgen is looking
at "solid mid-single-digit growth, although clearly an obesity win could
move this into double-digit growth territory," Morningstar analyst Karen
Anderson said.
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An injection pen of Zepbound, Eli Lilly’s weight loss drug, is
displayed in New York City, U.S., December 11, 2023. REUTERS/Brendan
McDermid/File Photo
A weight-loss drug launch from Amgen
would not happen before 2026, she said. The company, which reports
quarterly results on Tuesday, declined to comment on a timeline.
Companies including Novo Nordisk, Structure Therapeutics and recent
Roche acquisition Carmot Technologies, are developing dual GLP-1/GIP
"agonists," the term scientists use to describe a chemical that
activates a receptor to initiate a biological response.
Lilly's head of diabetes and metabolic research, Ruth Gimeno, in an
email said the company has "a high level of confidence in GIP
agonism."
Dr. Louis Aronne, director of Weill Cornell Medicine's weight
control center and a Novo trial investigator, said there is a theory
that turning the receptor both on and off works for weight loss
because GIP stimulation may eventually cause the receptors to stop
working.
"No one really understands why they both work," he said.
Dr. Caroline Apovian, co-director at Brigham and Women's Hospital
Center for Weight Management and Wellness, said it could also be
that GIP allows more GLP-1 receptors to open up.
Amgen's approach is rooted in linking a GLP-1 component to an
antibody that inhibits GIP, Honarpour explained.
"Our construct allows different pharmacology... When we give our
last dose, the effects seem to be prolonged," he said.
Morningstar's Anderson said GIP antagonism could cause issues with
insulin and she will examine the Phase 2 data when available for how
the drug effects blood sugar levels.
There have also been questions about MariTide's effect on bone
mineral density. Amgen has not seen an association, but the current
study is tracking that, Honarpour said.
"Obesity is the disease that causes all of the others," Apovian
said. "We need a wide array of options."
(Reporting By Deena Beasley; Editing by Caroline Humer and Bill
Berkrot)
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