Bisphosphonate Clinical Studies

Bisphosphonate clinical studies have shown promising anti-myeloma effects. A large Phase III trial in the United Kingdom showed that Zometa compared to a weak oral bisphosphonate (clodronate) had an anti myeloma effect. Zometa was not only superior to clodronate in its impact on skeletal problems but also significantly improved overall survival by an average of 5.5 months in patients with bone disease (50 months with Zometa vs. 44.5 months with clodronate). The beneficial effect of Zometa on overall survival could not be explained by bone effects alone, raising the possibility that the drug may have other favorable anti myeloma effects. There is much laboratory data to support the direct, indirect and immune-based anti-myeloma effects of Zometa.

How are bisphosphonates being studied in clinical trials?

A large national study is evaluating whether Zometa can be given less frequently—once every 3 months versus once a month. The goal of this study is to determine if less frequent dosing is safer than the standard dose as well as to compare the effectiveness of these two schedules.

In addition, due to a possible anti myeloma effect, Zometa is being studied in combination with Thalomid (an anti-myeloma drug) in early stage multiple myeloma to determine whether or not this combination is more effective than Thalomid alone in slowing the progression of myeloma.

What new bone drugs are in development?

A new drug available for treatment of bone disease is Xgeva (denosumab, Amgen). Xgeva is not a bisphosphonate. It is a novel agent approved by the FDA for many types of cancer, but it is not approved for use in multiple myeloma.

This drug was compared with Zometa in a Phase III trial of 1,756 people with advanced cancers, including 190 patients with multiple myeloma. Overall, the study showed that Xgeva was similar to Zometa in preventing bone complications. However, mortality was significantly higher among the myeloma patients treated with Xgeva. The limited number of myeloma patients in this study makes it difficult to definitively determine its effect. As a result, a larger randomized trial is now planned to evaluate monthly Xgeva compared to Zometa.

There are other new drugs in early stage clinical development (Phase I or Phase II) that may have the ability to not just strengthen bones but to also re-build them. They include ACE-011 and BHQ880.