Bayer HealthCare has announced that the company has submitted a marketing authorisation application to the European Medicines Agency (EMA) for radium-223 dichloride (radium-223) for the treatment of castration-resistant prostate cancer (CRPC) patients with bone metastases.
“This submission reflects our commitment to developing innovative cancer treatments for patients for whom only limited therapy options are available today,” said Kemal Malik, MD, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “With its novel mode of action and the proven survival benefit, radium-223 represents an innovation in the treatment of prostate cancer and is an important example of our growing oncology portfolio.”
The submission is based on data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. In the study, radium-223 significantly increased overall survival by 44% (HR=0.695, p=0.00007), resulting in a 30.5% reduction in the risk of death compared to placebo. The median overall survival (OS) benefit in patients with radium-223 was 3.6 months, based on 14.9 months OS with radium-223 plus best standard of care (BSoC) versus 11.3 months with placebo plus BSoC. These updated results were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June 2012.
The most common haematologic adverse events for patients treated with radium-223 and best standard of care (BSoC) and compared to placebo and BSoC included anaemia (31% versus 31%), neutropenia (5% versus 1%) and thrombocytopenia (12% versus 6%). With respect to Grade 3 and 4 adverse events, the most common events included anaemia (13% versus 13%), neutropenia (2% versus 1%) and thrombocytopenia (6% versus 2%). The most common non-haematologic adverse events in patients treated with radium-223 and BSoC compared to placebo and BSoC included bone pain (50% versus 62%), nausea (36% versus 35%), diarrhoea (25% versus 15%) and vomiting (19% versus 14%). With respect to Grade 3 to 4 adverse events, the most common events included bone pain (21% versus 26%).
About the ALSYMPCA trial
The ALSYMPCA trial was a Phase III, randomised, double-blind, placebo-controlled international study comparing radium-223 dichloride vs. placebo in symptomatic CRPC patients with bone metastases treated with BSoC compared with placebo plus BSoC. The trial enrolled 921 patients in more than 100 centres in 19 countries. The study treatment consisted of up to six intravenous administrations of radium-223 or placebo each separated by an interval of four weeks.
The primary endpoint of the study was overall survival. Secondary endpoints included time to occurrence of skeletal related events (SRE), changes and time to progression in PSA and ALP, safety, and impact on quality of life measures.
About CRPC and bone metastases
Prostate cancer is the most common non-cutaneous malignancy in men worldwide. In 2008, an estimated 899,000 men were diagnosed with prostate cancer and 258,000 died from the disease worldwide. Prostate cancer is the sixth leading cause of death from cancer in men.
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 radium-223 dichloride
Radium-223 dichloride (radium-223), formerly referred to as Alpharadin, is a therapeutic alpha particle-emitting pharmaceutical with targeted anti-tumour effect on bone metastases in development for CRPC patients with bone metastases.
In September 2009, Bayer signed an agreement with Algeta ASA (Oslo, Norway) for the development and commercialisation of radium-223. Under the terms of the agreement, Bayer will develop, apply for global health authority approvals, and commercialise radium-223 globally. Algeta will co-promote radium-223 with Bayer in the US. The ALSYMPCA trial was initiated by Algeta in June 2008.
Radium-223 is an investigational agent and is not approved by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), or other health authorities.
In terms of further development activities for radium-223, Bayer intends to conduct studies in earlier settings of prostate cancer, including combination studies with other agents, as well as exploratory studies in other tumours such as breast cancer and osteosarcoma.