Cambridge, UK, (26^th July 2011) – Amgen has announced that the European Commission (EC) has granted marketing authorisation for XGEVA^®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 tumours. 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. The primary goal of treatment for bone metastases is to prevent the occurrence of these debilitating and costly SREs.

The approval of denosumab marks an important development in the treatment of patients with bone metastases. Skeletal-related events caused by bone metastases may severely compromise a cancer patient’s quality of life through debilitating pain which may interfere with their ability to work, walk or even take care of themselves,” said Dr Amit Bahl, Consultant Clinical Oncology, Bristol.  “Denosumab offers sustained protection from SREs, combined with a delay in the progression of pain, which means denosumab has the potential to make a real difference to the lives of UK patients with advanced cancer.”

The marketing authorisation 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 tumour 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 tumours 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 <0.0001)). In this analysis, denosumab was also superior to zoledronic acid 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 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. Hypocalcaemia 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.”

About Denosumab

Denosumab is the first and only fully human RANK Ligand inhibitor approved in the EU for the prevention of SREs (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with bone metastases from solid tumors. Denosumab is the first novel bone metastases treatment for advanced cancer patients in more than a decade.

Denosumab is a fully human monoclonal antibody that binds to RANK Ligand, a protein essential for the formation, function and survival of osteoclasts (the cells that break down bone). Denosumab prevents RANK Ligand from activating its receptor, RANK, on the surface of osteoclasts, thereby decreasing bone destruction.

Denosumab is delivered as an every four week 120 mg subcutaneous injection.

Denosumab Regulatory Status

Denosumab is currently approved in the United States (U.S.) for the prevention of SREs in patients with bone metastases from solid tumours. Denosumab was approved following a six month priority review by the U.S Food and Drug Administration (FDA). In the U.S., denosumab is not indicated for the prevention of SREs in patients with multiple myeloma.ⁱ Denosumab 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.

Amgen has also submitted marketing applications for denosumab 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 2010. In addition, Amgen and GlaxoSmithKline (GSK) have a collaboration agreement for the commercialisation of denosumab in a number of countries where Amgen does not currently have a commercial presence. In these countries, marketing applications are filed by GSK.

Denosumab Important Safety Informationⁱ

Pre-existing hypocalcaemia must be corrected prior to initiating therapy with denosumab.

Patients with severe renal impairment (creatinine clearance < 30ml/min) or receiving dialysis are at greater risk of developing hypocalcaemia. Monitoring of calcium levels in these patients is recommended. If hypocalcaemia occurs while receiving denosumab, additional short-term calcium supplementation may be necessary.

Osteonecrosis of the jaw (ONJ) was reported in patients treated with denosumab. ONJ was confirmed in 1.8 percent of patients treated with denosumab and 1.3 percent of patients treated with zoledronic acid. Patients who are suspected of having or who develop ONJ while on denosumab should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Skin infections (predominantly cellulitis) leading to hospitalisation have been reported more frequently in patients receiving XGEVA (0.9%) compared with zoledronic acid (0.7%).

Most common (≥1/10, ≥1/100 to < 1/10) adverse reactions in patients receiving denosumab included dyspnoea, diarrhea, tooth extraction, hyperhidrosis, hypocalcaemia, hypophosphataemia and osteonecrosis of the jaw (ONJ).

Bone Metastases and SREs: Prevalence and Impact

Up to 64 percent of untreated patients with bone metastases experience devasting SREs ⁱⁱand are most commonly associated with cancers of the prostate, lung and breast, with incidence rates as high as 90 percent of patients with metastatic disease.^iii,iv,v,vi

Events considered to be SREs include fractures, spinal cord compression and severe bone pain that may require surgery or radiation.^viiSuch events can profoundly disrupt a patient’s life and can cause disability and pain.^viii,ix,x

About Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realise the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit http://www.amgen.co.uk.

Contact: Amgen

Emma Gilbert +44 (0) 7983 179507 – egilbert@amgen.com

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   DMO-GBR-AMG-249-2011
   

   Date of preparation: June 2011