Xofigo

Generic Name: radium 223 dichloride
Date of Approval: May 15, 2013
Company: Bayer HealthCare Pharmaceuticals Inc.

Treatment for: Advanced Prostate Cancer

FDA Approves Xofigo

The U.S. Food and Drug Administration (FDA) has approved Xofigo (radium 223 dichloride) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease. Xofigo is the first alpha particle-emitting radioactive therapeutic agent approved by the FDA that has demonstrated improvement in overall survival (OS) and delay in time to first symptomatic skeletal event (SSE) compared to placebo, as shown in the pivotal Phase III ALSYMPCA trial.

Efficacy and Safety Data Supporting Xofigo Approval

The approval of Xofigo (radium 223 dichloride, radium 223) is based on data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. At the interim analysis, radium 223 significantly improved overall survival (OS) [HR=0.695 (95% CI 0.552-0.875), p=0.00185]; median OS was 14.0 months with radium 223 plus best standard of care vs. 11.2 months with placebo plus best standard of care. Additionally, at the interim analysis there was a delay in the time to first symptomatic skeletal event (SSE) for patients treated with radium 223 vs. placebo.

Slideshow: Flashback: FDA Drug Approvals 2013

An updated analysis, conducted after the study was unblinded, showed a further improvement in overall survival (OS) for patients treated with radium 223 vs. placebo, with a median OS of 14.9 months vs. 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 radium 223 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.

About Xofigo (radium 223 dichloride) Injection

Xofigo with the active ingredient radium 223 dichloride (radium 223) is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect on bone metastases. Radium 223 mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of alpha emitters may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium 223 is less than 100 micrometers, which may limit damage to the surrounding normal tissue.

About the ALSYMPCA Trial

The ALSYMPCA trial was a Phase III, randomized, double-blind, placebo-controlled international study of radium 223 dichloride with best standard of care vs. placebo with best standard of care in symptomatic CRPC patients with bone metastases. The trial enrolled 921 patients in more than 100 centers in 19 countries. The study treatment consisted of up to six intravenous injections of radium 223 or placebo each separated by an interval of four weeks.

The primary endpoint of the study was overall survival (OS). A key secondary endpoint was time to first symptomatic skeletal event (SSE), as defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.

Highlights of Prescribing Information

Indications and Usage

Xofigo is an alpha particle-emitting radioactive therapeutic agent indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Dosage and Administration

The dose regimen of Xofigo is 50 kBq (1.35 microcurie) per kg body weight, given at 4 week intervals for 6 injections.

Dosage Forms and Strengths

Single-use vial at a concentration of 1,000 kBq/mL (27 microcurie/mL) at the reference date with a total radioactivity of 6,000 kBq/vial (162 microcurie/vial) at the reference date.

Contraindications

Pregnancy.

Warnings and Precautions

Bone Marrow Suppression: Measure blood counts prior to treatment initiation and before every dose of Xofigo. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after treatment. Monitor patients with compromised bone marrow reserve closely. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care measures.

Xofigo side effects

The most common adverse drug reactions (≥ 10%) in patients receiving Xofigo were nausea, diarrhea, vomiting, and peripheral edema.

The most common hematologic laboratory abnormalities (≥ 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.

To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See also: Side effects (in more detail)

Patient Counseling Information

Advise patients:

  • To be compliant with blood cell count monitoring appointments while receiving Xofigo. Explain the importance of routine blood cell counts. Instruct patients to report signs of bleeding or infections.
  • To stay well hydrated and to monitor oral intake, fluid status, and urine output while being treated with Xofigo. Instruct patients to report signs of dehydration, hypovolemia, urinary retention, or renal failure / insufficiency.
  • There are no restrictions regarding contact with other people after receiving Xofigo. Follow good hygiene practices while receiving Xofigo and for at least 1 week after the last injection in order to minimize radiation exposure from bodily fluids to household members and caregivers. Whenever possible, patients should use a toilet and the toilet should be flushed several times after each use. Clothing soiled with patient fecal matter or urine should be washed promptly and separately from other clothing. Caregivers should use universal precautions for patient care such as gloves and barrier gowns when handling bodily fluids to avoid contamination. When handling bodily fluids, wearing gloves and hand washing will protect caregivers.
  • Who are sexually active to use condoms and their female partners of reproductive potential to use a highly effective method of birth control during treatment and for 6 months following completion of Xofigo treatment.
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