223Ra-Radium Dichloride (223Ra-Xofigo® previously known as 223Ra-Alpharadin), is a 223Ra radioactive salt developed for the treatment of cancer types that commonly metastasize to the bone. While previous radio-therapeutics were used only for pain palliation, phase III trials of radium 223Ra dichloride demonstrated a positive effect on overall survival (OS), thereby establishing a truly therapeutic indication.

223Ra-Xofigo is approved in more than 40 countries including the United States (May 2013), the European Union and in Japan (since March 2016) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease

223Ra mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The cytotoxic effect is a consequence of the high linear energy transfer of 223Ra that causes double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The Alpha particle range from 223Ra is less than 100 µm (2 – 10 cell diameters) which may limit the damage to the surrounding normal tissue while remaining very efficient against tumor cells.

The ALSYMPCA clinical trial (921 patients, 100 centers, 19 countries) that supported the US FDA and European EMA approval showed that 223Ra significantly reduced the risk of death by 30.5% compared to Placebo. This overall survival (OS) benefit was observed both in patients who were treated with the chemotherapy docetaxel prior to study enrollment and in those who were not. The study treatment consisted of six intravenous injections of 223Ra or Placebo each separated by an interval of 4 weeks. Median OS was 14.9 months with 223Ra plus best standard of care vs. 11.3 months with Placebo plus best standard of care.

Target/Mechanism: Bone

Leading Emitter: Alpha particle (α)