SAN DIEGO — The investigational parathyroid-hormone–related protein (PTHrP) analog abaloparatide (Radius Health) significantly reduced fractures in high-risk postmenopausal women with osteoporosis, a key phase 3 study has shown.
Findings from the 18-month randomized, double-blind placebo-controlled Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial of more than 2000 women were presented March 5 here at the annual meeting of the Endocrine Society, ENDO 2015, by Paul Miller, MD, of the Colorado Center for Bone Research, Lakewood.
Abaloparatide was associated with an 86% reduction in vertebral fracture incidence — the primary end point — compared with placebo.
While that effect was similar to the 80% reduction in vertebral-fracture rate seen with the currently available osteoanabolic PTHrP analog teriparatide (Forteo, Eli Lilly), abaloparatide produced significantly greater reductions in nonvertebral fractures compared with both placebo and teriparatide. Moreover, abaloparatide was associated with significantly less hypercalcemia than was teriparatide.
"Patients at high risk of fracture could substantially benefit from treatment with abaloparatide based upon the results of the ACTIVE study," Dr Miller told Medscape Medical News.
Session comoderator Laura Maria Calvi, MD, PhD, from the University of Rochester Medical Center, New York, told Medscape Medical News, "The data didn't show a significant difference between the two [active comparators] for overall fractures but certainly suggest abaloparatide is at least as good as teriparatide in that setting.
"But the effect in the wrist is unique to abaloparatide, which is very exciting.…We don't see an improvement in the distal radius with teriparatide," she added.
Dr Miller explained that abaloparatide results in significant increases in bone formation but only a modest rise in bone resorption (assessed by markers). "This is consistent with the mechanism of action of selective binding to the PTHR1 receptor and may suggest that the 'anabolic window' is different from what has been shown for teriparatide."
In the ACTIVE trial, 2463 postmenopausal women were randomized to receive 18 months of 80-µg daily subcutaneous abaloparatide, injected placebo, or open-label injected 20-µg teriparatide. All the patients also received calcium and vitamin D supplements; 1901 participants completed the trial.
The patients had a mean age of 69 years and mean body mass index of 25 kg/m2. Nearly half (47%) had had a previous nonvertebral fracture, and a third had experienced one or more vertebral fractures. Mean baseline T-scores at the spine, femoral neck, and total hip were -2.90, -2.14, and -1.90, respectively.
At 18 months, the rate of new vertebral fractures among the 690 patients on abaloparatide was 0.58%, a reduction of 86% compared with the 4.2% rate seen in the 711 placebo patients (P < .0001). For the 717 receiving teriparatide, the 0.84% vertebral-fracture rate represented an 80% reduction from placebo (P < .0001), Dr Miller reported.
Abaloparatide produced a significant 43% reduction in the rate of nonvertebral fractures (2.7% vs 4.7% with placebo, P = .0489) and 45% fewer clinical fractures (3.9% vs 8.3% with placebo, P = .0112), whereas the rates of nonvertebral and clinical fractures with teriparatide did not differ significantly from placebo (P = .2157 and .1127, respectively).
Wrist Fractures "Difficult to Treat"
Wrist fractures 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%).
Dr Calvi told Medscape Medical News, "The distal radius is very challenging to treat. This has been a site where we don't do very well with treatment. [Abaloparatide] would be unique."
Bone-mineral density increased with both drugs compared with placebo at the spine, femoral neck, and hip at 6, 12, and 18 months (P < .0001 for all comparisons), but abaloparatide increased bone density significantly more than did teriparatide at the hip, femoral neck, and spine at most time points during the 18-month study, Dr Miller noted.
Common adverse events that did not differ between the two drugs were back pain, arthralgia, upper-respiratory-tract infection, hypercalciuria, and dizziness.
The one major difference was seen in hypercalcemia (based on albumin-corrected serum calcium measured 4 hours pre- and postinjection), which was significantly less for abaloparatide than for teriparatide, 3.41% vs 6.36% (P = .00555), compared with 0.37% with placebo (P < .0001 for both).
"Many osteoporotic patients, based upon the data, could benefit in reducing their fracture risk based upon the results of ACTIVE," Dr Miller reiterated.
Dr Calvi told Medscape Medical News, "This is a really new tool that could be very exciting. We have many choices in the bisphosphonate category, but we have very little in the bone anabolic category of treatments."
Radius Health plans to file a new drug application with the US Food and Drug Administration and a marketing authorization application in the European Union in the second half of this year.
The study was funded by Radius Health, and Dr Miller is a paid principal investigator. Disclosures for the coauthors are listed in the abstract. Dr Calvi has reported no relevant financial relationships.
ENDO 2015: The Endocrine Society 97th Annual Meeting. Abstract LB-OR01-3, presented March 5, 2015.
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Cite this: Novel Agent Abaloparatide Reduces Fractures, Including Wrist - Medscape - Mar 06, 2015.