ORLANDO, Florida — More data on the investigational anabolic agent for osteoporosis abaloparatide (Radius Health) have been reported, with the investigator of the trial saying this drug, if/when approved, will be of most use for postmenopausal women who are at really high risk of nonvertebral fractures in particular.
Here at ENDO 2017: The Endocrine Society Annual Meeting, Michael McClung, MD, of Oregon Osteoporosis Center, Portland, presented a new subanalysis from the 18-month, randomized, double-blind placebo-controlled ACTIVE trial involving over 2400 women, showing no differences in response to abaloparatide by geographic region.
A separate post hoc analysis also showed that the effects of once-daily subcutaneous abaloparatide vs placebo on fracture risk reduction were similar for women of Hispanic/Latino ethnicity compared with other women enrolled in ACTIVE.
Abaloparatide is an anabolic agent for osteoporosis that is awaiting approval in the United States — a decision had been expected by the end of last month, but Radius Health recently announced that a ruling is now anticipated by June 30, as the Food and Drug Administration (FDA) has requested additional time to review information on the drug.
At the end of Dr McClung's talk at the meeting, one of the chairs of the session asked: "When you look at the overall data for this new type of [osteoporosis] product compared with the ones on the market, do you feel like the difference in fractures is clinically significant?"
He replied, "Oh boy!" but then proceeded to give his overall take on the drug.
"It appears that there is a consistently somewhat better effect, and in particular — although we didn't show this, but it's in the paper — in the time to onset of fracture protection, it seems to be faster with abaloparatide," Dr McClung said.
"So that the whole story has a consistency to it — less increases in bone resorption and faster, numerically greater increases in bone-mineral density."
He did concede, however, that "for vertebral fractures, I think the differences are very small — all the [osteoporosis] drugs are really, really good at protecting patients from vertebral fracture." It appears from ACTIVE that it is in the realm of nonvertebral fractures that abaloparatide "shows some superiority," he noted.
Decision on Abaloparatide Approval Pushed Back
Asked by Medscape Medical News if he was concerned about the slight delay to the decision date on abaloparatide in the United States, Dr McClung said: "No. The FDA is overwhelmed. We have not had any new bone drugs for 7 years and suddenly we have two" [referring also to romosozumab, an investigational humanized monoclonal antibody that inhibits sclerosin, developed by Amgen/UCB].
Findings from the pivotal trial with abaloparatide, ACTIVE, were initially presented at ENDO 2015. At the end of the 18-month trial, daily subcutaneous injection of abaloparatide was associated with an 86% reduction in the incidence of vertebral fracture, the primary end point of the trial, compared with placebo, and the results were later published in the Journal of the American Medical Association (2016;316:722-733).
In ACTIVE, a third group of women were randomized to open-label teriparatide [Forteo/Forsteo, Lilly], another osteoanabolic agent, for 18 months, but the data on teriparatide were not included in the primary-end-point calculation.
Teriparatide is the only anabolic agent for osteoporosis currently on the market, approved almost 15 years ago, and Dr McClung told Medscape Medical News that, if approved, abaloparatide will compete directly with the former, as the two agents "are cousins."
In the European Union, biosimilars of teriparatide have recently been recommended for approval (Movymia [STADA Arzneimittel] and Terrosa [Gedeon Richter]), which the European Medicines Agency says have shown "comparable quality, safety, and efficacy" to the reference product, Forsteo.
Abaloparatide is also awaiting approval in the European Union.
How Are Nonvertebral Fractures, Specifically "Wrist," Defined?
Overall in ACTIVE, abaloparatide produced a significant 43% reduction in the rate of nonvertebral fractures (2.7% vs 4.7% with placebo, P = .0489) whereas the rates of nonvertebral fractures with teriparatide did not differ significantly from placebo (P = .2157).
And for wrist (distal-radius) fractures specifically, these were significantly lower in the abaloparatide group compared with teriparatide (0.5% vs 2.0%, P = .0149), although neither achieved statistical significance compared with placebo (1.5%).
At the time of presentation of these findings in 2015, it was observed by the chair of the session that "the effect in the wrist is unique to abaloparatide, which is very exciting."
After Dr McClung's ENDO 2017 presentation, one audience member noted that "we were very excited to see a reduction in nonvertebral fractures in ACTIVE," but she observed that "going into detail," it appears that, in some osteoporosis trials, "wrist" fractures include ulnar fracture as well as that of the distal radius, and she asked him to comment on how this could be interpreted.
He acknowledged that "one of the huge problems in our field is the lack of consistency in the definition of what nonvertebral fractures are, and [the fact that] different studies have defined them in different ways."
"We are still trying to tweak and squeeze as much efficacy on therapies for nonvertebral fractures as we can, and that's where I think abaloparatide appears — from the only study we have so far [ACTIVE] — to have some superiority," he noted.
"How clinically significant that is depends on the risk of the patient," he added.
"For a patient at really high risk for nonvertebral fracture, then the relative difference in risk protection could be very meaningful. For lower risk patients — those in whom we'd be less likely to consider an anabolic drug — then the difference is really not very great."
Dr McClung reports receiving consulting fees from Amgen, Merck, and Radius. Disclosures for the coauthors are listed in the abstract.
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ENDO 2017. April 1, 2017; Orlando, Florida. Abstract OR08-7
Medscape Medical News © 2017
Cite this: Abaloparatide Best in 'Really High-Risk' Osteoporosis Patients - Medscape - Apr 06, 2017.