Thousand Oaks: 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 per cent 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.
Amgen shares are up more than 30 per cent over the past year, closing at an all-time high of $323 on Friday, compared with an 8 per cent 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.
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.”