Amgen Pushes Ahead With ‘Son of Dmab’ For Treating Broken, Frail Bones

Folks who follow Amgen closely know there’s really been one main theme to this story the past couple years—Dmab, Dmab, Dmab. Also know as denosumab, this is the targeted antibody drug Amgen developed for bone disorders that is supposed to be biggest thing to emerge from its internal R&D pipeline in about 20 years (although that’s not saying much because there were a lot of lean times).

The Thousand Oaks, CA-based company (NASDAQ: AMGN), which has significant R&D operations in South San Francisco, Seattle, and Cambridge, MA, won two coveted FDA approvals for denosumab last year—the drug is now sold under the name Prolia for osteoporosis, and as Xgeva to fight bone fractures in cancer patients. Combined sales could reach $2 billion in 2013, according to analyst Eun Yang of Jefferies & Co. That’s real money even to a company as huge as Amgen, with $15.1 billion in sales last year.

Still, there’s another side to the bone R&D story at Amgen that fewer people have noticed. Amgen has a drug that you might call the “son of Dmab” advancing through its clinical trial pipeline. It’s made to work in a completely different way than denosumab, and could offer physicians with a one-two punch against bone disorders. If clinical trials for this drug, AMG785, pan out this year, Amgen could be in position to grab an even greater share of the $9 billion-dollar-plus osteosporosis market as some of the old workhorse drugs turn generic.

“It’s appropriate to focus on Dmab because of the impact it will have on patients and the company in two big indications, but it has taken away focus from everything else we’re doing, and everything else we’re doing is very interesting,” says Amgen’s chief medical officer, Sean Harper. He adds: “Between dmab and this sclerostin program, we dominate the excitement in the bone field. To the key opinion leaders in the bone field, dmab is old hat for them. They are all focused on sclerostin.”

Sean Harper

It takes a little bit (not much, I promise) of science to understand what Harper is talking about with sclerostin, and why it matters.

First off, healthy people maintain a constant balance of what scientists call bone remodeling, in which bone is broken down and rebuilt in response to both injuries and normal wear and tear. Cells known as osteoclasts work to break down bone, while another kind of cell, osteoblasts, build up new bone. The two cell types have a yin-yang relationship, but when that cycle falls out of balance, it can lead to bone loss, Amgen scientist Bill Dougall explained in this October 2008 feature story.

Denosumab is designed to work by blocking a protein called RANK Ligand which activates the osteoclasts. So essentially, the drug works by preventing excessive breakdown of bone, and giving osteoblast cells enough breathing space to do their thing and build up bone.

But Amgen has long been interested in the other side of the equation—the osteoblasts themselves. That’s where the protein called sclerostin comes into the picture. Sclerostin works against … Next Page »

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3 responses to “Amgen Pushes Ahead With ‘Son of Dmab’ For Treating Broken, Frail Bones”

  1. There’s actually more of a local Seattle connection to this story than I realized. John Latham discovered the sclerostin gene and did some of the early work on the AMG785 antibody while he was at Celltech R&D in Bothell (now part of UCB, Amgen’s collaborator). John is now the chief scientific officer of Alder Biopharmaceuticals, another antibody company in Bothell. Thanks to Alder’s Mark Litton for the heads up.

  2. Luke,
    For full disclosure and to give credit to the entire Celltech Seattle Facility, there were many scientist who helped discover the sclerostin gene and antibody. But you are correct Alder’s management team with John Latham led the effort.
    Thanks for the clarification.

    Mark Litton

  3. I didn’t mean to wade into this issue of who made the key scientific discoveries in this business story. But, of course, John Latham wasn’t the only person involved in important early work that occurred at Celltech R&D in Bothell, as a couple of readers have helpfully pointed out. You can see a more complete list of authors in this 2001 paper in the American Journal of Human Genetics.