ORLANDO, Fla. — Three new nonbisphosphonate agents for the treatment of osteoporosis are anticipated, according to a speaker here.
Rachel Pessah-Pollack, MD, FACE, outlined the pathophysiology underlying the promising new therapeutic agents and discussed some of the data regarding the risks and benefits of the new resorptive agents.
“Clearly, there is a need for other osteoporosis treatments,” she said. “Perhaps an ideal agent would be an oral therapy. Medications not linked to rare side effects would also be helpful as many patients will not take treatments that could lead to them. Convenience and cost-effectiveness also needs to be addressed.”
The possible new agents include odanacatib, a cathepsin K inhibitor being developed by Merck; romosozumab, a sclerostin inhibitor from Amgen and UCB; and Radius Health’s abaloparatide, a recombinant pathyroid hormone-related protein.
Much of the data on the new agents have yet to be published, Pessah-Pollack said.
Preliminary trial results for odanacatib show that as a once-weekly oral medication, the agent was effective in increasing bone mineral density in the spine and hip, reducing fracture in the spine, hip and nonvertebral areas. Efficacy was not affected by food intake.
“Inhibiting cathepsin K does provide a potentially efficacious and unique mechanism of action to treat osteoporosis with moderate bone resorption and minimal bone formation effects,” Pessah-Pollack said. “This unique mechanism of action with inhibition of bone resorption does not decrease osteoblast number or activity.”
Preliminary data on romosozumab have shown that bone formation occurs rapidly after the first dose is given, and mild suppression of C-terminal telopeptide (CTX) and total procollagen type 1 N-terminal propeptide (P1NP) is increased in the early stages of receiving the medication.
“Romosozumab increases the bone density of the lumbar spine, total hip and femoral neck,” Pessah-Pollack said. “It had a rapid transitory increase in bone formation with mild suppression of bone resorption. We currently have phase 3 fracture trials ongoing with completion expected later this year.”
In preliminary results from the ACTIVE study comparing abaloparatide vs. placebo or Forteo (teriparatide, Lilly USA) in postmenopausal women at high risk for fracture, the primary outcome was to evaluate the incidence of new vertebral fractures.
Treatment with abaloparatide resulted in an 85% reduction in new vertebral fractures, more than 40% reduction in both nonvertebral fractures and incidental vertebral fractures. There was a modest rise in bone resorption and bone formation markers with abaloparatide compared with teriparatide.
“Abaloparatide does have a significant reduction in incidence of new vertebral fractures vs. nonvertebral fractures compared with placebo,” Pessah-Pollack said. “It does appear slightly more efficacious than teriparatide, but we need more data and need the data to be published and all of the results be available.”
Data over the next year for these potential treatments look promising, Pessah-Pollack said.
“The question is going to be how we’re going to incorporate this into what we’re currently doing,” she said. – by Amber Cox
Pessah-Pollack R. Beyond oral bisphosphonates for postmenopausal osteoporosis D sequential drug therapy: What’s next on the horizon? Presented at: AACE Annual Scientific and Clinical Congress; May 25-29, 2016; Orlando, Fla.
Disclosure: Pessah-Pollack reports being a speaker for Boehringer Ingelheim.