Alpharadin
Encyclopedia
Alpharadin is an experimental radiopharmaceutical under clinical evaluation to improve survival in patients with bone metastases from advanced cancer. It is being developed by the Norwegian company Algeta ASA, in a partnership with Bayer
. Phase III clinical trials showed a 2.8 months increase in median overall survival due to the drug as compared to placebo (the increase was from 11.2 months to 14.0 months).
Alpha radiation has a very short range of 2-10 cells (when compared to current radiation therapy
which is based on beta or gamma radiation), and therefore causes less damage to surrounding healthy tissues (particularly bone marrow). Radium-223 has a half life of 11.4 days, making it ideal for targeted cancer treatment. Furthermore, any Alpharadin that is not taken up by the bone metastases is rapidly cleared to the gut and excreted.
or other effects.
Alpharadin successfully met the primary endpoint of overall survival in the phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer patients) study for bone metastases resulting from castration-resistant prostate cancer (CRPC) in 922 patients.
The ALSYMPCA study was stopped early after a pre-planned efficacy interim analysis, following a recommendation from an Independent Data Monitoring Committee, on the basis of achieving a statistically significant improvement in overall survival (two-sided p-value = 0.0022, HR = 0.699, the median overall survival was 14.0 months for Alpharadin and 11.2 months for placebo). Earlier Phase II of the trial showed 4.5 months increased survival. The lower figure of 2.8 months increased survival in phase III, is a probable result of stopping the trail. Survival time for the patients still alive could not be calculated.
Algeta and Bayer are preparing to file regulatory submissions in the U.S and Europe and will discuss pricing with the relevant authorities.
Alpharadin also showed promising preliminary results in a phase IIa trial with bone metastases resulting from breast cancer that no longer responds to endocrine therapy. The data showed that Alpharadin reduced the levels of bone alkaline phosphatase (bALP) and urine N-telopeptide (uNTX), key markers of bone turnover associated with bone metastases in breast cancer. Alpharadin was also found to be safe and well tolerated.
In clinical trials, Alpharadin was administered by intravenous injection once a month for 4 or 6 months. Alpharadin can be prepared and shipped for use anywhere around the world.
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
. Phase III clinical trials showed a 2.8 months increase in median overall survival due to the drug as compared to placebo (the increase was from 11.2 months to 14.0 months).
Mechanism of action
Alpharadin uses alpha radiation from radium-223 decay to kill cancer cells. Radium-223 naturally self-targets to bone metastases by virtue of its properties as a calcium-mimic.Alpha radiation has a very short range of 2-10 cells (when compared to current radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
which is based on beta or gamma radiation), and therefore causes less damage to surrounding healthy tissues (particularly bone marrow). Radium-223 has a half life of 11.4 days, making it ideal for targeted cancer treatment. Furthermore, any Alpharadin that is not taken up by the bone metastases is rapidly cleared to the gut and excreted.
Trials
The phase II study of bone metastases in CRPC patients found no AnemiaAnemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
or other effects.
Alpharadin successfully met the primary endpoint of overall survival in the phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer patients) study for bone metastases resulting from castration-resistant prostate cancer (CRPC) in 922 patients.
The ALSYMPCA study was stopped early after a pre-planned efficacy interim analysis, following a recommendation from an Independent Data Monitoring Committee, on the basis of achieving a statistically significant improvement in overall survival (two-sided p-value = 0.0022, HR = 0.699, the median overall survival was 14.0 months for Alpharadin and 11.2 months for placebo). Earlier Phase II of the trial showed 4.5 months increased survival. The lower figure of 2.8 months increased survival in phase III, is a probable result of stopping the trail. Survival time for the patients still alive could not be calculated.
Algeta and Bayer are preparing to file regulatory submissions in the U.S and Europe and will discuss pricing with the relevant authorities.
Alpharadin also showed promising preliminary results in a phase IIa trial with bone metastases resulting from breast cancer that no longer responds to endocrine therapy. The data showed that Alpharadin reduced the levels of bone alkaline phosphatase (bALP) and urine N-telopeptide (uNTX), key markers of bone turnover associated with bone metastases in breast cancer. Alpharadin was also found to be safe and well tolerated.
In clinical trials, Alpharadin was administered by intravenous injection once a month for 4 or 6 months. Alpharadin can be prepared and shipped for use anywhere around the world.