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Novel Bone Drug (odanacatib, cathepsin K inhibitor) Found Safe After Four Years
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By Michael Smith, North American Correspondent, MedPage Today
Published: October 20, 2010
Action Points
* Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
* Explain to interested patients that the investigational osteoporosis drug odanacatib, a cathepsin K inhibitor, was safe and well tolerated and yielded increases in bone mineral density.
* Note that the rate of adverse events was 79% in the odanacatib arm and 70.1% among placebo patients, while the rates of serious adverse events were 9% and 14.6%, respectively.
TORONTO -- The investigational osteoporosis drug odanacatib was safe and well tolerated over four years, a researcher said here.
The drug, a cathepsin K inhibitor, also yielded continued increases in bone mineral density, according to Neil Binkley, MD, of the University of Wisconsin Madison.
There was also a "prompt" response -- loss of bone mineral density -- when patients stopped taking it, Binkley reported at the annual meeting of the American Society for Bone and Mineral Research.
The findings come from a phase II study, which initially randomized patients to placebo or one of four doses of the drug for a two-year trial. In the third year of the study, patients were re-randomized to 50 milligrams a week of odanacatib or placebo.
In the fourth year -- which Binkley reported here -- patients who had been on placebo during the trial or who had been given the lowest dose of odanacatib (three mg a week) were switched to 50 mg a week of the drug. Other participants remained on their year-three assignment.
All told, the fourth year extension had 133 patients who completed the year, including 39 in the placebo arm, Binkley said, although subgroups -- according to treatment history -- tended to have small numbers. For instance, only 13 patients were on placebo in the original trial and the third year, before being switched to odanacatib for the fourth year.
Binkley reported that the rate of adverse events was 79% in the odanacatib arm and 70.1% among placebo patients, while the rates of serious adverse events were 9% and 14.6%, respectively -- higher among the placebo patients.
Only four patients -- all in the odanacatib arm -- dropped out because of adverse events, Binkley said. There were more adverse events involving the skin in the odanacatib arm -- 9% versus 4.9% -- but there were no cases of scleroderma or morphea-like lesions, he said.
"There's really not much of a safety signal here," Binkley said.
The efficacy data was divided according to treatment history and the primary endpoint was bone mineral density in the lumbar spine.
The researchers found:
* For patients who had been on 50 mg of odanacatib for four years, spinal bone mineral density continued to rise, reaching 10.7% higher than baseline. In the fourth year, they experienced an average increase of 2.8%.
* For those who had been on the drug and were switched to placebo, there was a "prompt loss" that left patients only 0.4% above baseline on average.
* For those who had been on placebo and were switched to the drug, there was a 4.8% increase, similar to what had been seen in the original trial.
Results were similar in other anatomic sites, Binkley said, with the exception of the distal forearm, where bone mineral density was maintained among patients on four years of the drug.
The drug also yielded a "sustained reduction" in markers of bone resorption and "modest" drops in markers of bone formation that tended toward baseline over time, he said.
The key finding was the fact that the drug appeared to have little or no effect on skin, according to Lorenz Hofbauer, MD, of the Dresden Technical University Medical Center in Dresden, Germany, who was not part of the study but who moderated the session at which it was presented.
"You don't want to use an osteoporosis drug that damages your skin," he told MedPage Today.
But Hofbauer cautioned that the numbers in the trial are small and said that a large phase III trial now under way will be more definitive.
One element of the drug that has both positive and negative aspects, he said, is its "on-off effect." The prompt resolution of the effect when patients stopped the drug means that it is easily reversible, which could be important in some circumstances.
On the other hand, if patients fail to take their medication, they'll quickly be left without protection, he said. "It's not something that has an effect once you stop taking it," Hofbauer said.
Clinicians, he said, will have to wait and see if the current phase III study yields similar results and -- most importantly -- whether it has any effect on fracture rates.
The study was supported by Merck.
Binkley reported financial links with Merck.
Hofbauer had no disclosures.
Primary source: American Society for Bone and Mineral Research
Source reference:
Binkley N, et al "Effect of odanacatib on bone density and bone turnover markers in postmenopausal women with low bone mineral density: Year 4 results" ASBMR 2010; Abstract 1247.
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