latest on denosumab (alternate to bisphosphonates)

[Lani]

I have posted that I had been hearing/reading good things about denosumab

It is FDA approved for osteoporosis, but not yet for bone mets from Breast or Prostate cancer (although it may be close)

Here is the latest:


ASBMR: Long-Term Use of Bone Drug Safe, Efficacious

Extended use of the osteoporosis drug denosumab (Prolia) is safe and continues to be efficacious, a researcher said here.

In the first two years of an open-label extension to the randomized FREEDOM trial, bone mineral density continued to increase, while the rate of adverse events did not, according to Socrates Papapoulos MD, PhD, of Leiden University Medical Center in Leiden, the Netherlands.

And the rate of fractures among the 4,450 participants remained low, Papapoulos reported here at the annual meeting of the American Society for Bone and Mineral Research.


The FREEDOM study enrolled more than 7,000 women with osteoporosis and randomly assigned them to 60 milligrams of denosumab, injected subcutaneously every six months, or a matching placebo. After three years, all forms of fractures were markedly reduced in patients taking denosumab, a fully human monoclonal antibody to RANKL, which is involved in breaking down bone.

But there was some concern that serious skin infections were increased in the denosumab patients.

To investigate the long-term effects, all participants in the original study were allowed to continue, with those in the placebo arm switching to denosumab. All told, 2,343 denosumab patients continued, as did 2,207 participants in the placebo arm.

"The most significant finding, was the continued increase in bone mineral density in years four and five."

Specifically, he reported, women who had the full five years of treatment saw lumbar spine and total hip bone mineral density increase 13.7% and 7%, respectively, over baseline. The switched patients -- the "de novo" group -- saw increases similar to those reported in the first two years of the randomized trial, he said.

As well, the drug continued to result in low fracture rates. The annualized incidence of new vertebral fractures was 1.4%, while new nonvertebral fractures occurred at rates of 1.2% and 1.1% in years four and five, respectively.

The researchers also found no major changes in the incidence and types of adverse events and serious adverse events. Specifically, the rates of adverse events per 100-subject-years in the first three years, compared with the extension, were:

39.8 versus 33.3 for infections
1.3 compared with 1.1 for eczema
Zero versus less than 0.1 for hypocalcemia
A key finding was that the rate of serious infections fell, from 1.8 per 100 subject-years in the randomized trial to 1.4 in the extension. Malignancies were much the same, at 2.0 versus 2.1 per 100 subject-years.

There were no cases of osteonecrosis of the jaw among denosumab patients in the trial or in the two years following, although there were two cases in the de novo group, Papapoulos reported, and no cases of atypical fracture.

The extension data -- especially those on adverse events -- are reassuring, according to Elizabeth Shane, MD, of Columbia University in New York City, a bone specialist who was not involved in the research.

Clinicians had been concerned, she said, about what appeared to be an excess of serious skin infections among those taking denosumab in the randomized part of the study. The lack of such a signal in the extension is "giving us some reassurance," she told MedPage Today.

The efficacy data, she said, are no surprise: "As you would expect, the drug continues to exert its effects," she said.

The study was supported by Amgen. Papapoulos reported financial links with Amgen, Merck, Novartis, Lilly, Procter & Gamble.

Shane reported financial links with Eli Lilly, Merck, Novartis, and Amgen.


Primary source: American Society for Bone and Mineral Research
Source reference:
Papapoulos A, et al "Four years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first year extension of the FREEDOM trial" ASBMR 2010; Abstract 1025.