Bayer Announces that the New England Journal of Medicine Publishes Results from Phase III ALSYMPCA Study of Radium 223 Dichloride

• Significant overall survival benefit observed with radium 223 in patients who received prior treatment with docetaxel and in those who did not
• Radium 223 significantly delayed time to first symptomatic skeletal event
• All main secondary efficacy endpoints with radium 223 were met, showing clinical benefit with radium 223 in patients with castration-resistant prostate cancer and symptomatic bone metastases

TORONTO, July 18, 2013 /CNW/ - Bayer HealthCare today announced that data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial of its drug radium 223 dichloride (radium 223) in castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases and no known visceral metastatic disease are published in the July 18 issue of the New England Journal of Medicine (NEJM). These data supported the U.S. Food and Drug Administration (FDA) approval of Xofigo injection in May 2013.

In ALSYMPCA, radium 223 reduced the risk of death by 30.5 per cent compared to placebo, a significant risk reduction (HR=0.695). This overall survival (OS) benefit was observed in patients who were treated with the chemotherapy docetaxel prior to study enrollment and in those who were not. All patients in the study were treated with best standard of care in addition to radium 223 or placebo. Researchers performed both a pre-planned interim analysis (n=809) and an updated analysis (n=921) in this study. The overall survival benefit was the same in both analyses.

"The quality of life and overall survival benefits observed with radium 223 represent real progress for patients, as bone metastases can be painful and lead to death in men with CRPC," explained Christopher Parker, MD, Consultant in Clinical Oncology at The Royal Marsden Hospital and The Institute of Cancer Research, London, and principal investigator of ALSYMPCA. "These data showing significantly improved overall survival, regardless of prior treatment with chemotherapy, add to our knowledge about the potential use and benefit of radium 223 in these patients."

According to the Canadian Cancer Society, prostate cancer accounts for about one-quarter (26%) of all new cancer cases in men in this country.ⁱ  "These results are very promising and represent an important step forward in improving the quality of life for men with prostate cancer," says Christian Lauterbach, President & CEO of Bayer Inc. in Canada. "Bayer continues to advance the oncology treatment landscape in Canada and is excited by the data and what it will mean for the prostate cancer community."

In September 2009, Bayer signed an agreement with Algeta ASA (Oslo, Norway) for the development and commercialization of radium 223. Under the terms of the agreement, Bayer will develop, apply for health authority approvals worldwide and commercialize radium 223 globally. Algeta US, LLC is co-promoting radium 223 with Bayer in the U.S.

About the ALSYMPCA Trial and its Results
The ALSYMPCA trial was a Phase III, randomized, double-blind, placebo-controlled international study of radium 223 dichloride vs. placebo in patients with CRPC, symptomatic bone metastases and no known visceral metastatic disease. The trial enrolled 921 patients in more than 100 centers in 19 countries. Patients were stratified based on whether or not they had received docetaxel prior to study enrollment. The study treatment consisted of best standard of care and up to six intravenous injections of radium 223 or placebo each separated by an interval of four weeks.

The primary endpoint of the study was overall survival (OS). A key secondary endpoint was time to first symptomatic skeletal event (SSE). SSE was defined as first use of external beam radiation therapy to relieve skeletal pain, new symptomatic pathologic bone fracture, occurrence of spinal cord compression or tumour-related orthopedic surgical intervention.

The OS impact of radium 223 was consistent in both patients who received treatment with docetaxel prior to study enrollment and in those patients who did not receive prior docetaxel treatment. In the interim analysis, radium 223 reduced the risk of death by 25 per cent (HR=0.755) compared to placebo in patients who received prior docetaxel treatment and by 39 per cent (HR=0.611) compared with placebo in those who did not. In the updated analysis, radium 223 reduced the risk of death by 29 per cent (HR=0.710) compared with placebo in those who were given prior docetaxel and by 26 per cent (HR=0.745) compared with placebo in those who were not.

Radium 223 significantly improved OS in the overall study population at the interim analysis (HR=0.695, p=0.00185); median OS was 14 months with radium 223 plus best standard of care vs. 11.2 months with placebo plus best standard of care. These findings were supported by the updated analysis in which radium 223 showed the same significant improvement in OS (HR=0.695; median OS was 14.9 vs. 11.3 months).

The main secondary endpoints in the ALSYMPCA trial provide further support for the efficacy of radium 223. In the interim analysis, radium 223 significantly prolonged the time to the first symptomatic skeletal event (SSE) compared with placebo (median 15.6 months vs. 9.8 months, respectively; HR=0.658, p<0.001).

In addition, radium 223 significantly delayed the time to alkaline phosphatase (ALP) progression (HR=0.167, p<0.00001) and time to prostate-specific antigen (PSA) progression (HR=0.643, p<0.00001). These are two important biomarkers for CRPC with bone metastases; ALP is a marker that indicates bone health, and PSA is a marker often used to track prostate cancer disease progression. Similar results were observed in the updated analysis.

The number of patients experiencing adverse events was lower in the radium 223 group compared with the placebo group (558/600 [93 per cent] vs. 290/301 [96 per cent]). Most adverse events associated with radium 223 were mild to moderate. The most common adverse drug events (greater than or equal to 10 per cent) in patients receiving radium 223 were diarrhea, nausea, vomiting and thrombocytopenia. Grade 3 and 4 treatment-emergent adverse events were reported among 56.5 per cent of radium 223-treated patients and 62.5 per cent of placebo-treated patients. The most common hematologic laboratory abnormalities (greater than or equal to 5 per cent) were anemia, thrombocytopenia and neutropenia.

About Radium 223 Dichloride
Radium 223 is an alpha particle-emitting radioactive therapeutic agent with an anti-tumour effect on bone metastases. The active ingredient is the alpha particle-emitting isotope radium-223, which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of radium 223 may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumour effect on bone metastases. The alpha particle range from radium 223 is less than 100 micrometers, which may limit damage to the surrounding normal tissues.

Radium 223 is approved in the United States and is marketed under the brand name Xofigo^® for the treatment of patients with CRPC, symptomatic bone metastases and no known visceral metastatic disease. Market authorization in Canada has not yet been obtained for Radium 223 for the treatment of CRPC.

About CRPC and Bone Metastases
Prostate cancer is the most common non-cutaneous malignancy in men worldwide. In Canada, an estimated 26,500 new cases of the disease will be diagnosed and 4,000 men will die of prostate cancer in 2013.ⁱⁱ One in 7 Canadian men will develop prostate cancer during his lifetime and 1 in 28 will die of it.ⁱⁱⁱ

A majority of men with CRPC have radiological evidence of bone metastases. Once the cancer cells settle in the bone, they interfere with bone strength, often leading to pain, fracture and other complications that can significantly impair a man's health. Bone metastases secondary to prostate cancer typically target the lumbar spine, vertebrae and pelvis. In fact, bone metastases are the main cause of morbidity and death in patients with CRPC.

About Bayer Inc.
Bayer Inc. is a Canadian subsidiary of Bayer AG and the headquarters for the Canadian operations.  Celebrating its 150 anniversary, Bayer AG is an international research-based group with core businesses in healthcare, crop science and innovative materials committed to creating a better life for all through science.

In Canada, Bayer operates its healthcare business - Pharmaceuticals, Consumer Care, Diabetes Care, Animal Health and Radiology & Interventional - from its headquarters in Toronto, ON and its CropScience business from Calgary, AB.

With more than 1,300 employees across the country, in 2012, Bayer had sales of $1.6 billion CDN and invested $55.9 million CDN in research and development in Canada. Globally, Bayer AG had sales of $39.8 billion Euro and invested $3 billion Euro in research and development. For more information about Bayer Inc., please visit www.bayer.ca.

Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

REFERENCES
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ⁱ http://www.cancer.ca/en/cancer-information/cancer-101/canadian-cancer-statistics-publication/?region=on
ⁱⁱ http://ca.movember.com/mens-health/prostate-cancer/
ⁱⁱⁱ http://ca.movember.com/mens-health/prostate-cancer/

SOURCE: Bayer Inc.

For further information:

Emily Hanft, Bayer
[email protected]
416-240-5466

Ethan Pigott, beSPEAK Communications
[email protected]
416-558-2783