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Study Says Amgen's Denosumab Beats Fosamax in Bone Density....Hello Genisi

BioWorld Today - May. 21, 2008
http://www.therapeuticsdaily.com/news/article.cfm?contenttype=sentryarticle&contentvalue=1783789&channelID=28

Preliminary results of a Phase III study showed that Amgen Inc.'s osteoporosis drug denosumab significantly increased bone-mineral density (BMD) at the total hip in postmenopausal women who switched from using Merck & Co.'s Fosamax (alendronate).

The relative magnitude of BMD improvement at the total hip was about 80 percent greater in the denosumab group vs. the Fosamax group, said Amgen spokeswoman Kerry Beth Daly.

Patients who received twice-yearly subcutaneous injections of 60-mg denosumab also achieved significantly greater BMD gains at the lumbar spine, femoral neck, distal radius and hip trochanter compared with the group that continued on weekly 70-mg Fosamax therapy, Daly told BioWorld Today.

"The p-values for all of the sites and BMD gains were quite significant," she added.

The 504-patient, one-year study, known as STAND, is the second Phase III head-to-head trial that showed that denosumab, a fully human monoclonal antibody that targets RANK ligand, an essential regulator of osteoclasts, resulted in BMD gains vs. Fosamax.

The results of the earlier Phase III DECIDE study, which involved about 1,200 patients, showed that the relative magnitude of BMD improvement at the total hip was about 40 percent greater in the denosumab vs. the Fosamax group.

Amgen plans to present the full data from the STAND trial later this year at a medical meeting of bone experts and will publish the study results shortly thereafter, Daly said, noting that the firm was required to release the preliminary data this week to fulfill its Securities and Exchange Commission requirements and obligations.

Analysts speculated that the full STAND results will be presented in September at the annual meeting of the American Society for Bone and Mineral Research. Amgen said that neoplasm and infection adverse events in the STAND trial were "well balanced" between the denosumab and Fosamax treatment groups.

"This is important, as the many Street observers have worried about infection risk," said Mark Schoenebaum, an analyst with Bears Sterns.

Analysts had expressed concern about denosumab after results of Amgen's DEFEND study showed that eight patients who received the drug were hospitalized with infections, including pneumonia. (See BioWorld Today, April 4, 2008.)

However, researchers concluded that none of the infections were related to the drug.

Analyst Michael Aberman, of Credit Suisse Securities LLC, called the preliminary results from the STAND trial an "incremental positive" for denosumab.

"While there is no guarantee that the BMD improvement will translate into fracture reduction, we think it is likely that dmab shows comparable, if not better, fracture reduction than bisphosphonates," he said in a research note.

Although the BMD increase in patients treated with denosumab in the STAND trial seems robust, said analyst William Tanner, of Leerink Swann Research, extrapolation to whether the drug will reduce hip fractures "should be done with caution."

Analysts noted that the big news for denosumab will come when Amgen releases results of its large Phase III FREEDOM study about the impact of the drug on fracture risk reduction in women with postmenopausal osteoporosis.

Those results are due to be released in the second half of this year, Daly said.

In addition to osteoporosis, Amgen is testing denosumab as a therapy for patients with rheumatoid arthritis and cancer treatment-induced bone loss in patients with breast and prostate cancers.

The company also is examining the potential of the drug to delay bone metastases and inhibit and treat bone destruction across several stages of cancer.

Amgen will be presenting several sets of data later this month about the drug in the oncology setting at the annual meeting of the American Society of Clinical Oncologists, including results of two Phase II studies that describe the effects of denosumab on markers of bone destruction in patients with bone metastases from prostate and breast cancers who were previously treated with intravenous bisphosphonates.

"When patients were switched to denosumab, they achieved greater results above and beyond what was achieved on other therapies," Daly said.

"Those results were found regardless of the underlying disease, regardless of the type of bisphosphonates and regardless of the dose of the bisphosphonates," she noted.

Amgen's drug had a better effect than bisphosphonates in the oncology and osteoporosis studies because denosumab's ligand inhibitor mechanism of action "targets all osteoclasts wherever they are found in bone tissue and throughout the skeleton and at all stages of formation and function," Daly maintained.

Whereas researchers believe that bisphosphonates target only the fully mature osteoclasts found on the bone surface, she explained