The pharmaceutical company Amgen recently announced that its new drug Prolia ^[1] more effectively prevents bone pain and fractures in patients with advanced bone disease than Zometa ^[2]. Prolia was noted to have higher efficacy in patients with various types of cancers, including multiple myeloma. The announcement followed the presentation of results from recent Phase 3 trials at the European Society of Medical Oncology Annual Meeting. 

Bone disease is frequently associated with multiple myeloma and can cause bone pain and lead to serious bone complications, such as lesions and fractures, that are collectively referred to as skeletal-related events, or SREs.

The current standard of care for the prevention of SREs are bisphosphonates. The two most commonly used bisphosphonates in multiple myeloma are Zometa (zoledronic acid) and Aredia ^[3] (pomidronate).

Recently, several alternative drug therapies have been evaluated for the prevention of SREs in cancer patients. One of these new preventive drugs is Prolia (denosumab), a human monoclonal antibody that specifically targets a protein that regulates the cells responsible for the breakdown of bone.

Amgen compared the efficacies of Prolia and Zometa in three Phase 3 trials. The trials included more than 5,700 patients with multiple myeloma or breast cancer, prostate cancer, or other solid tumor bone metastases. Patients received either 120 mg of Prolia or 4 mg of Zometa every four weeks.

An integrated analysis of the three studies found that in comparison to Zometa, Prolia more effectively delayed time to the first SRE. The median time to the first SRE was 27.7 months for Prolia and 19.5 months for Zometa. The overall disease progression and survival rates were comparable for both treatment groups. 

The frequency of side effects was similar in both groups and consistent with previous studies. Patients who received Prolia did not experience as many kidney-related side effects, but many of them experienced low serum calcium levels.

According to Dr. Ravi Vij of Washington University in St. Louis, the decrease in calcium levels is not concerning and may even be beneficial for multiple myeloma patients. “Hypercalcemia [elevated calcium levels] is often a problem in patients with myeloma,” said Dr. Vij in email correspondence with The Beacon. He added that future studies may show that the calcium-level-reducing effects of Prolia could help bring calcium to normal levels in myeloma patients.

A separate survey-based analysis of the three clinical trials suggested that Prolia more effectively prevented bone pain than Zometa. Patients assessed the severity of their pain (range 0 to 10) in a Brief Pain Inventory on a monthly basis throughout the study.

Patients treated with Prolia had a median of 181 days before reporting worsening of clinically significant pain, compared to 169 days for patients treated with Zometa.

While the results of these clinical trials seem promising for Prolia, Dr. Vij pointed out that it is too early to predict Prolia’s future influence on the standard of care for bone pain and SREs. “The data set comparing the efficacy of Zometa with Prolia is very limited,” stated Dr. Vij. “An adequately powered study needs to be done in order to answer this question.”

For more information, please refer to the Amgen press release ^[4].