Denosumab approved in Europe

19 Jul 2011

Amgen today announced that the European Commission (EC) has granted marketing authorization for denosumab for the prevention of skeletal-related events (SREs) (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with bone metastases from solid tumors.

This approval of denosumab applies to all 27 European Union (EU) member states. The EC also granted denosumab an additional year of data and market exclusivity in the EU since the indication was considered new for denosumab and based on the significant clinical benefit of denosumab in comparison with existing therapies.

Bone metastases, the spread of cancer to the bones, are a common and serious concern for patients with advanced cancer and present a burden to the healthcare system. Weakened bones due to metastases can lead to SREs. The primary goal of treatment for bone metastases is to prevent the occurrence of these debilitating and costly SREs.

"Skeletal-related events associated with bone metastases are truly devastating and painful for patients living with cancer, and today's approval of denosumab marks a real advance," said Professor Ingo J. Diel, M.D., Institute for Gynecological Oncology, SPGO, Mannheim, Germany. "In clinical trials denosumab demonstrated sustained protection from SREs and also delayed the progression of pain. These factors will make a genuine difference in the lives of patients living with advanced cancer."

The marketing authorization for denosumab is based on three pivotal, Phase 3 head-to-head trials that evaluated the effectiveness of denosumab versus zoledronic acid at delaying SREs. The SRE clinical program for denosumab spanned more than 50 tumor types in over 5,700 patients.

In the SRE trials, denosumab demonstrated a clinically meaningful improvement in preventing SREs compared to zoledronic acid. In these trials, denosumab  was administered every four weeks as a 120 mg subcutaneous injection, versus zoledronic acid delivered every four weeks via a 15-minute intravenous infusion, with adjustments for kidney function per the requirements of the zoledronic acid prescribing information.

In patients with breast or prostate cancer and bone metastases, denosumab  was superior to zoledronic acid in reducing the risk of SREs. In patients with bone metastases due to other solid tumors or multiple myeloma, denosumab was non-inferior to zoledronic acid in reducing the risk of SREs.

In an integrated analysis of all three studies denosumab was superior to zoledronic acid in delaying time to first on-study SRE by 17 percent or 8.2 months (median time to first skeletal related event of 27.6 months for denosumab and 19.4 months for zoledronic acid, (p

In patients with mild or no pain at baseline, time to worsening pain was delayed for denosumab compared to zoledronic acid (198 versus 143 days) (p=0.0002). The time to pain improvement was similar for denosumab  and zoledronic acid in each study and the integrated analysis.

Overall rates of adverse events and serious adverse events were generally similar between denosumab and zoledronic acid. Osteonecrosis of the jaw (ONJ) was seen in approximately 1-2 percent of patients, with no statistically significant difference between treatment arms. Hypocalcemia was more frequent in the denosumab treatment group. Overall survival and progression-free survival were similar between arms in all three trials.

"Today's approval of denosumab marks the culmination of many years of research and innovation by Amgen scientists, beginning with the discovery of the RANK Ligand pathway and the understanding of its role in bone biology to the development of the denosumab oncology clinical program," said Willard H. Dere, M.D., senior vice president and international chief medical officer at Amgen. "denosumab promises to make a real difference for patients with cancer whose daily lives are affected by the consequences of bone metastases."


Source: Amgen