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 underway 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.”
