Data presented as part of Presidential Session featuring best and late-breaking abstracts at 2011 European Multidisciplinary Cancer Congress revealsthat the investigational drug radium-223 chloride (Alpharadin, Bayer HealthCare Pharmaceuticals and Algeta ASA) showed positive results in the Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial.

The study met its primary endpoint by significantly improving overall survival by 44% (p=0.00185, HR=0.695) in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. All of the main secondary efficacy endpoints analyzed to date were met, including delay in skeletal-related events (SREs). The data was presented during the Presidential Session at the 2011 European Multidisciplinary Cancer Congress in Stockholm, Sweden (Abstract No. 1LBA: Presidential Session I: Best and Late Breaking Abstracts, Saturday, September 24, 2011.

CRPC and bone metastases
Prostate cancer is the most common cancer among men in the United States and other developed countries (other than skin cancer). Approximately 15% of prostate cancer cases are considered regional or distant, which means that the cancer has spread beyond the prostate to nearby or distant areas of the body (metastasis).

CRPC is also known as hormone-refractory prostate cancer (HRPC). 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 and overall quality of life. Bone metastases secondary to prostate cancer typically target the lumbar spine, vertebrae and pelvis. Bone metastases are the main cause of disability and death in patients with CRPC.

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Overall survival
The data showed that patients who were treated with radium-223 chloride had a median overall survival of 14 months compared to 11.2 months for the placebo group. Time to first SREs (13.6 months vs. 8.4 months, 64% improvement, HR=0.610, p=0.00046). Total alkaline phosphatase (ALP) normalization (33% vs. 1% of patients, p<0.001), and a 49% improvement in time to prostate-specific antigen (PSA) progression (HR=0.671, p=0.00015).

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Non-hematologic adverse events
The most common non-hematologic adverse events (occurring in at least 15% of patients) included bone pain (43% vs. 58%), nausea (34% vs. 32%), diarrhea (22% vs. 13%), constipation (18% vs. 18%) and vomiting (17% vs. 13%); and the most common hematologic adverse events included anemia (27% vs. 27%) for patients receiving radium-223 chloride as compared to placebo. With respect to Grade 3 to 4 adverse events, the most common events included bone pain (18% vs. 23%) for patients receiving radium-223 chloride as compared to placebo. Following a pre-planned interim analysis, the company agreed with the Independent Data Monitoring Committee’s (IDMC) recommendation to stop the study and offer patients on the placebo arm treatment with radium-223 chloride.

Demonstrating survival benefit
Radium-223 chloride is an investigational drug in development for cancer patients with bone metastases and is not approved by the FDA, the European Medicines Agency (EMA), or other health authorities. “Radium-223 chloride is the first bone-targeted, alpha-emitting, radiopharmaceutical to demonstrate a survival benefit in men with castration-resistant prostate cancer and symptomatic bone metastases,” said Oliver Sartor, M.D., Tulane Medical School, New Orleans, and an ALSYMPCA trial investigator.

Radium-223 chloride was recently granted Fast Track designation by the U.S. Food and Drug Administration (FDA). The Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The company plans to file a New Drug Application with the FDA for radium-223 chloride in mid-2012.

Trial Design
The ALSYMPCA trial is a Phase III, randomized (2:1), double-blind, placebo-controlled international study of radium-223 chloride plus current standard of care compared with placebo plus current standard of care in patients with symptomatic CRPC that has spread to the bone. The primary endpoint of the study is overall survival. Secondary endpoints include time to occurrence of SREs, changes and time to progression in PSA and ALP, safety, and impact on quality of life measures. The trial enrolled 922 patients in more than 100 centers in 19 countries who have histologically or cytologically confirmed adenocarcinoma of the prostate, known hormone refractory disease, multiple skeletal metastases (greater than or equal to 2 hot spots) on bone scintigraphy, no intention to use cytotoxic chemotherapy within the next 6 months and either regular (not occasional) analgesic medication use for cancer-related bone pain or treatment with EBRT for bone pain. The initial trial was initiated by Algeta ASA (Oslo, Norway) in June 2008.

For more information:
– Abstract 1LBA: Parker C, et al “Overall survival benefit of radium-223 chloride (Alpharadin) in the treatment of patients with symptomatic bone metastases in castration-resistant prostate cancer: A phase III randomized rial (ALSYMPCA)” ECCO-ESMO 2011 (European Multidisciplinary Cancer Congress).
– Abstract #7008, Poster Session Genitourinary Malignancies – Prostate Cancer: Sten Nilsson(Karolinska Institute, Stockholm, Sweden)”Twenty-four-month Safety Data From Phase II Studies of Radium-223 Chloride, a First-in-class Alpha-pharmaceutical With a Highly Favorable Safety Profile for Patients With Castration-resistant Prostate Cancer (CRPC) and Bone Metastases (Sunday 25 September, 14.00-16.30, CEST).

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