Algeta announced that updated data from the phase III trial, ALSYMPCA, for its investigational drug Alpharadin (radium-223 dichloride). The data confirmed the overall survival of men with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases using Alpharadin, compared to the interim analysis from June 2011.
• Overall survival in Alpharadin arm increased by 44%
• Median survival benefit increased to 3.6 months
• Significantly delayed time to first skeletal-related event (SRE)
• Submissions seeking marketing approval in US & Europe expected in 2H 2012
The updated data showed that Alpharadin improved overall survival by 44% (p=0.00007, HR=0.695), resulting in a 30.5% reduction in the risk of death compared to placebo. The median overall survival benefit with Alpharadin was 2.8 months at the time of the interim analysis in June 2011 and 3.6 months in this updated analysis (14.9 months in patients given Alpharadin vs. 11.3 months with placebo). These data was presented as a late-breaking abstract in an oral abstract session on June 5, 2012 at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL. (LBA No. 4512).
Dr. Chris Parker of The Royal Marsden NHS Foundation Trust, London, and The Institute of Cancer Research, London, and principal investigator of ALSYMPCA trial said, “Bone metastases are one of the main causes of disability and death in patients with castration-resistant prostate cancer, yet until now there has been little progress made towards developing therapies that target the cancer when it has spread to the bone. “Alpharadin is the first therapy specifically addressing cancer that has spread to the bone that has shown, in a phase III trial, to significantly improve overall survival.”
In addition to improving overall survival, radium-223 dichloride led to a statistically significant delay in the time to first skeletal-related event (SRE).
The safety profile for Alpharadin was consistent with previous study results. The most common hematologic adverse events included anemia (31% vs. 31%), neutropenia (5% vs 1%) and thrombocytopenia (12% vs. 6%) for patients receiving Alpharadin compared to placebo. With respect to Grade 3 and 4 adverse events, the most common events included anemia (13% vs. 13%), neutropenia (2% vs. 1%) and thrombocytopenia (6% vs. 2%). The most common non-hematologic adverse events included bone pain (50% vs. 62%), nausea (36% vs. 35%), diarrhea (25% vs. 15%), and vomiting (19% vs. 14%) for patients receiving Alpharadin as compared to placebo. With respect of Grade 3 to 4 adverse events, the most common events included bone pain (21% vs. 26%).
Alpharadin has been granted Fast Track designation by the US Food & Drug Administration (FDA). Bayer plans to file Alpharadin seeking marketing approval for CRPC with regulatory authorities in the US and Europe based on the ALSYMPCA data in the second half of 2012. In terms of further development activities, Bayer intends to conduct studies in earlier settings of prostate cancer, including combination studies with other agents, as well as undertaking exploratory studies in other tumors such as breast cancer and osteosarcoma.
The presentation slides shown at ASCO are available to download at www.algeta.com.
Joel T Nowak, M.A., M.S.W.
I wonder which drug is better, alpharadion or XL-184 (if I remember the name correctly)
both work against bone metastases, but by totally different mechanisms of action I suppose
if both drugs get approved, what will be the drug of choise after a patient with stage IV prostate cancer progresses after the initial hormone therapy and docetaxel chemo?
I suppose the standard treatment will be then abiraterone or MDV 3100 (or TAK 700 in future) PLUS either aplharadin or XL 184
Pawel,
Two of the big questions that will need to be evaluated are the issues of surrounding both staging (ordering) and combining drugs. We really do’t have good answers back by good research. – Joel