Amgen (Nasdaq: AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended a positive opinion for the marketing authorization of XGEVA™ (denosumab) for the prevention of skeletal-related events (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with bone metastases from solid tumors. If approved by the European Commission, Amgen would receive marketing authorization for XGEVA in all European Union (EU) Member States. The CHMP also recommended to grant XGEVA an additional year of data and market exclusivity in the EU since the indication was considered significantly new for XGEVA, and based on the significant clinical benefit of the product 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 fractures and compression of the spinal cord and necessitate procedures like major surgery and radiation, collectively called skeletal-related events (SREs). The primary goal of treatment for bone metastases is to prevent the occurrence of these debilitating and costly SREs.
"A diagnosis of skeletal-related events associated with bone metastases is devastating for patients living with cancer, and our goal is to prevent the occurrence of these debilitating bone complications, which can disrupt a patient's life and cause disability, pain, and hospitalization," said Willard Dere, M.D., senior vice president and international chief medical officer, Amgen. "XGEVA provides patients with superior efficacy over Zometa in preventing skeletal-related events in patients with solid tumors and prolonging the time until pain worsens. XGEVA also offers the ease of every four weeks subcutaneous injection and no requirement for dose adjustment for changes in renal function. XGEVA has the potential to make a meaningful difference for patients with advanced cancer and their healthcare providers."
The CHMP positive opinion is based on three pivotal, Phase 3 head-to-head trials that evaluated the effectiveness of XGEVA versus Zometa® (zoledronic acid) at delaying SREs. The clinical program for XGEVA spanned more than 50 tumor types in over 5,700 patients. In the SRE trials, XGEVA demonstrated a clinically meaningful improvement in preventing SREs compared to Zometa.
Specifically, in patients with breast or prostate cancer and bone metastases, XGEVA was superior to Zometa in reducing the risk of SREs. In patients with bone metastases due to other solid tumors or multiple myeloma, XGEVA was non-inferior to Zometa in reducing the risk of SREs. In an integrated analysis of all three studies XGEVA was superior to Zometa 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 XGEVA and 19.4 months for Zometa, p <0.0001). In this analysis, XGEVA was also superior to Zometa in delaying time to first-and-subsequent on-study SRE by 18 percent (p<0.0001).
In patients with mild or no pain at baseline, time to worsening pain was delayed for XGEVA compared to Zometa (198 versus 143 days)>
In these double-blind trials, XGEVA was administered every four weeks as a 120 mg subcutaneous injection, versus Zometa delivered every four weeks via a 15-minute intravenous infusion, with adjustments for kidney function per the requirements of the Zometa prescribing information. XGEVA was not associated with renal toxicity or acute phase reactions, both well known side effects of Zometa treatment.
Overall rates of adverse events and serious adverse events were generally similar between XGEVA and Zometa. Osteonecrosis of the jaw (ONJ) was infrequent, with no statistically significant difference between treatment arms. Hypocalcemia was more frequent in the XGEVA treatment group. Overall survival and progression-free survival were similar between arms in all three trials.
XGEVA Regulatory Status
XGEVA is currently approved in the United States (U.S.) for the prevention of SREs in patients with bone metastases from solid tumors. XGEVA was approved following a six month priority review by the U.S. Food and Drug Administration (FDA). In the U.S., XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.(i) XGEVA is also approved in Canada for reducing the risk of developing SREs in patients with bone metastases from breast cancer, prostate cancer, non-small cell lung cancer, and other solid tumors. In Canada, XGEVA is not indicated for reducing the risk of developing SREs in patients with multiple myeloma.
Amgen has also submitted marketing applications for XGEVA in Australia, Mexico, Russia and Switzerland. In Japan, Amgen is working with its licensing partner, Daiichi Sankyo Company, Limited and a marketing application was submitted in August. In addition, Amgen and GlaxoSmithKline (GSK) have a collaboration agreement for the commercialization of XGEVA in a number of countries where Amgen does not currently have a commercial presence. In these countries, marketing applications are filed by GSK.
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