FDA approves Bayer’s Xofigo for treatment of prostate cancer

FDA has approved radium Ra 223 dichloride (Xofigo, Bayer) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. It is intended for men whose cancer has spread after receiving medical or surgical therapy to lower testosterone.

“What’s most important is the efficacy benefit to patients,” Shannon Campbell, vice president & general manager, oncology at Bayer HealthCare Pharmaceuticals told Formulary. “Xofigo is the first and only alpha particle-emitting radioactive therapeutic agent approved by FDA that has demonstrated improvement in overall survival [OS] and delay in time to first symptomatic skeletal event [SSE] compared to placebo. These are crucial benefits, as bone metastases are the main cause of morbidity and death in patients with CRPC.”

In addition, Xofigo is easy to administer - given as a patient-specific ready-to-use intravenous injection administered by a slow IV injection over 1 minute in an outpatient hospital or clinic setting,” Campbell added. “Patients may return home shortly after the Xofigo injection, with no restrictions on interpersonal contact.” 

Xofigo, or radium-223, mimics calcium and targets areas of high bone turnover at the site of bone metastases.  Essentially, it attacks a tumor where it lives in the bone while limiting damage to the surrounding normal tissues. 

In August 2012 FDA approved enzalutamide (Xtandi, Astellas and Medivation) to treat men with metastatic castration-resistant prostate cancer that has spread or recurred, even with medical or surgical therapy to minimize testosterone. Enzalutamide is approved for patients who have previously been treated with docetaxel.

According to the National Cancer Institute, prostate cancer is the most common cancer, other than non-melanoma skin cancer, and the second leading cause of cancer-related death in men in the United States. It is estimated that approximately $11.9 billion is spent each year in the United States on prostate cancer treatment.

Prostate cancer incidence rates rose dramatically in the late 1980s, when screening with the prostate-specific antigen (PSA) test, which received initial FDA approval in 1986, came into wide use. Since the early 1990s, prostate cancer incidence has been declining. Mortality rates for prostate cancer also have declined since the mid-1990s.

Xofigo is being approved more than 3 months ahead of the product’s prescription drug user fee goal date of August 14, 2013, the date the agency was scheduled to complete its review of the drug application. FDA reviewed Xofigo under the agency’s priority review program, which provides for an expedited review of drugs that appear to provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products.

The approval of Xofigo is based on data from the pivotal phase 3 ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. At the interim analysis, Xofigo significantly improved overall survival (OS) [HR=0.695 (95% CI, 0.552–0.875); P=.00185]; median OS was 14 months with Xofigo plus best standard of care versus 11.2 months with placebo plus best standard of care. In addition, at the interim analysis there was a delay in time to first symptomatic skeletal event (SSE) for patients treated with Xofigo versus placebo.

An updated analysis, conducted after the study was unblinded, showed improvement in overall survival (OS), with a median OS of 14.9 months versus 11.3 months; HR=0.695 (95% CI, 0.581–0.832).

The most common adverse reactions (greater than or equal to 10%) in patients receiving Xofigo in the ALSYMPCA trial were nausea, diarrhea, vomiting, and peripheral edema. The most common hematologic laboratory abnormalities (greater than or equal to 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.  

For a snapshot of prostate cancer go to: http://www.cancer.gov/researchandfunding/snapshots/prostate