Folks who follow Amgen
The Thousand Oaks, CA-based company, 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."
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 the osteoblasts that build up bone. So it stood to reason that if you could develop a precise antibody to block sclerostin, it would like unleashing osteoblasts to build up stronger, more dense bone material.
Amgen, along with collaborators at Belgium-based UCB, have developed AMG785 for that purpose. The companies were especially encouraged to plow ahead against this target by studies that looked at certain people with genetic defects that make them incapable of producing sclerostin. They are basically healthy -- they just have much more dense, fracture-resistant bones than most people, Harper says.
"We kind of know already what will happen if we inactivate sclerostin with a monoclonal antibody," Harper says.
Amgen has three mid-stage clinical trials under way that will give Harper and his team a much better idea if they can prove that hypothesis. A couple of these studies, in patients with broken legs, aim to see whether various doses of AMG785 help bones heal faster than when patients get a placebo. Another important study will look at older patients with osteoporosis, to see how much the Amgen drug helps improve bone mineral density compared with a placebo, or a tougher comparator -- Eli Lilly's teriparatide (Forteo).
Nobody on Wall Street will get very excited until they see convincing clinical results, but so far, based on animal studies, Amgen and bone research leaders are optimistic about AMG785, Harper says. "What we've seen already is the fastest, most robust increases in bone mineral density we've seen with any intervention in the bone field," he says.
If that can be confirmed in the ongoing studies, essentially you have one Amgen drug (denosumab) that prevents the excessive breakdown of bone, and then you would have another (AMG785) that triggers the fast rebuilding of bone. Amgen has considered whether to use them together, but Harper sought to downplay that idea, saying, "it might be too much" to give both drugs at once.
Amgen has a couple other ideas in mind for how the two drugs can go hand-in-hand. One idea is to take a severe osteoporosis patient and start them on AMG785, get their bone mineral density built up to a more acceptable level after a year or two, and then switch patients over to denosumab to keep them from relapsing into a state with fragile bone density, Harper says. Patients with mild to moderate osteoporosis might only need denosumab to keep them from getting worse, he says.
From a business perspective, if you have sales reps familiar with denosumab calling on docs who are familiar with denosumab, it's pretty simple to start selling one more drug to the same people. Mid-stage clinical trial results of the new drug's activity in osteoporosis patients should be available this year, offering Harper and his team a guide on how to go about running a Phase III program that it will need to win FDA approval. FDA approval is clearly years away, but maybe not as far away as some Amgen observers think, Harper says.
"It's early days," he says. "But we've got some really interesting things in the pipeline that are not way back in the preclinical pipeline, they are actually pretty far along."
More from Xconomy.com:
- Amgen's Dmab Faces FDA Delay
- Amgen's Dmab Wins FDA Approval
- Amgen Shows Off Cancer Drug Pipeline Before Scientific Meeting
- Amgen Wins FDA OK for Cancer Drug
Luke Timmerman is the National Biotech Editor of Xconomy, and the Editor of Xconomy Seattle. You can email him at [email protected], or follow him at twitter.com/ldtimmerman.
