An anabolic bone biologic now in a Phase 3 clinical trial has the potential to be a game-changer in osteoporosis therapy, according to Chad Deal, MD, who will present the ACR clinical symposium Osteoporosis Update on Tuesday afternoon.
Romosozumab offers increases in bone mass that are greater than currently available osteoporosis medications, said Dr. Deal, Head of the Center for Osteoporosis and Metabolic Bone Disease and Vice Chair for Quality and Outcomes in the Department of Rheumatology at the Cleveland Clinic. No fracture data are available at this time.
“I tell patients that the future, if that drug gets through clinical trials, is very promising for treating patients with severe osteoporosis,” said Dr. Deal, who said the hope is for romosozumab to be on the market in late 2017. “I think it is going to be a very effective medication.”
Other updates include:
- Results from the extension trial on denosumab show continued bone density increases that are greater than those seen with bisphosphonate therapy. Non-vertebral fracture reduction using a virtual twin analysis is robust.
- Data on abaloparatide, a parathyroid-hormone–related protein (PTHrP) analog, have been presented from a large Phase 3 RCT and show excellent fracture reduction with lower rates of hypercalcemia than teriparatide. Results from the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial were presented in abstract form at the Endocrine Society annual meeting in March.
- A daily patch to deliver PTH has shown excellent pharmacokinetics and increases in bone mass. One benefit of the patch, Dr. Deal said, is that – in addition to avoiding daily injections – the drug is lyophilized so it can be stored at room temperature. That feature makes it particularly beneficial for patients who travel, who can then pack it in their luggage and be on their way, he said.
Dr. Deal also expects to address the latest thinking regarding the so-called drug holiday for patients on bisphosphonate therapy.
Since 2011, he said, the U.S. Food and Drug Administration has required warning labels on the drugs about the risk of atypical femur fractures (AFF). The FDA warned of the increased risk of AFF and reported no advantage to continuing bisphosphonate therapy beyond five years.
Two of the major trials in this area that can inform decisions on the issue of drug holidays are the Fracture Intervention Trial Long-term Extension (FLEX), which published results in 2006, and the HORIZON-Pivotal Fracture Trial (PFT), which published results in 2012.
The FLEX trial compared the effects of discontinuing alendronate treatment after five years versus continuing for 10 years, and the HORIZON trial compared the effects of using zoledronate for three years versus six years. Both studies found fewer vertebral fractures in patients who took the drugs for longer periods of time. Patients that benefit from longer-term therapy include those with hip T-score
On the other hand, Dr. Deal said, “There are appropriate patients at low or moderate risk of fractures who have a good response to therapy, whose T-score is in the osteopenic range and who don’t have a history of previous fractures, in whom it’s appropriate to give a holiday after three to five years of therapy.”
Tuesday’s session will include a review of AFF based on last year’s updated guidance of the definition and treatment by the American Society for Bone and Mineral Research along with a discussion of osteonecrosis of the jaw (ONJ).
ONJ, a complication most common in cancer patients, does occur in osteoporosis patients taking antiresorptive medications. The main question for rheumatologists, Dr. Deal said, is how to handle patients on these medications who are planning to have oral surgery.