FDA Approves Denosumab for Bone Metastases

The Food and Drug Administration on Nov. 18 approved the monoclonal antibody denosumab (Xgeva) for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Denosumab maker Amgen made the announcement, which was expected since the agency was required to make a decision on the indication by Nov. 18. The drug was given a 6-month priority review, indicating that it was considered a major advance in treatment.

“Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer,” Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in a written statement on the approval.

A fully human monoclonal antibody with a unique mechanism of action, denosumab specifically targets the receptor activator of the nuclear factor kappa-B (RANK) ligand, the essential mediator of osteoclast fusion. The drug inhibits osteoclast formation, function, and survival, resulting in reduced bone resorption. The RANK ligand pathway was discovered by Amgen scientists in the mid-1990s, according to the company.

According to Amgen, bone metastases occur in 1.5 million cancer patients worldwide. They are most commonly seen in prostate, lung, and breast cancer. Denosumab was not approved for bone metastases related to multiple myeloma.

“A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating,” Amgen chairman and CEO Kevin Sharer said in a written statement. “We are pleased to offer this new advance to patients and their health care providers.”

The approval of denosumab was based on three phase III head-to-head trials comprising 5,700 patients that compared the drug with zoledronic acid (Zometa). The drug was superior to zoledronic acid in preventing skeletal-related events (SRE) in breast and prostate cancer. Some of that data was presented in June at the annual meeting of the American Society of Clinical Oncology. Denosumab was noninferior in preventing SREs in multiple myeloma and other solid tumors.

Adverse effects include hypocalcemia, fatigue, hypophosphatemia, and nausea. Osteonecrosis of the jaw can also occur.

The drug is given by subcutaneous injection once every 4 weeks. *

Because of the drug’s expense, Amgen is launching a new patient assistance program. The Xgeva First Step Coupon Program will provide assistance to eligible patients who need help meeting a deductible, copayment, or coinsurance. The first injection would be covered and subsequent injections would cost a maximum of $25.

Denosumab was approved in June to treat postmenopausal women with osteoporosis who are at high risk for fracture.

* CORRECTION, 11/19/2010: The original version of this article misstated the dosage frequency of denosumab (Xgeva). It is administered every 4 weeks as a subcutaneous injection. This version has been updated.

The Food and Drug Administration on Nov. 18 approved the monoclonal antibody denosumab (Xgeva) for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Denosumab maker Amgen made the announcement, which was expected since the agency was required to make a decision on the indication by Nov. 18. The drug was given a 6-month priority review, indicating that it was considered a major advance in treatment.

“Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer,” Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in a written statement on the approval.

A fully human monoclonal antibody with a unique mechanism of action, denosumab specifically targets the receptor activator of the nuclear factor kappa-B (RANK) ligand, the essential mediator of osteoclast fusion. The drug inhibits osteoclast formation, function, and survival, resulting in reduced bone resorption. The RANK ligand pathway was discovered by Amgen scientists in the mid-1990s, according to the company.

According to Amgen, bone metastases occur in 1.5 million cancer patients worldwide. They are most commonly seen in prostate, lung, and breast cancer. Denosumab was not approved for bone metastases related to multiple myeloma.

“A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating,” Amgen chairman and CEO Kevin Sharer said in a written statement. “We are pleased to offer this new advance to patients and their health care providers.”

The approval of denosumab was based on three phase III head-to-head trials comprising 5,700 patients that compared the drug with zoledronic acid (Zometa). The drug was superior to zoledronic acid in preventing skeletal-related events (SRE) in breast and prostate cancer. Some of that data was presented in June at the annual meeting of the American Society of Clinical Oncology. Denosumab was noninferior in preventing SREs in multiple myeloma and other solid tumors.

Adverse effects include hypocalcemia, fatigue, hypophosphatemia, and nausea. Osteonecrosis of the jaw can also occur.

The drug is given by subcutaneous injection once every 4 weeks. *

Because of the drug’s expense, Amgen is launching a new patient assistance program. The Xgeva First Step Coupon Program will provide assistance to eligible patients who need help meeting a deductible, copayment, or coinsurance. The first injection would be covered and subsequent injections would cost a maximum of $25.

Denosumab was approved in June to treat postmenopausal women with osteoporosis who are at high risk for fracture.

* CORRECTION, 11/19/2010: The original version of this article misstated the dosage frequency of denosumab (Xgeva). It is administered every 4 weeks as a subcutaneous injection. This version has been updated.

The Food and Drug Administration on Nov. 18 approved the monoclonal antibody denosumab (Xgeva) for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Denosumab maker Amgen made the announcement, which was expected since the agency was required to make a decision on the indication by Nov. 18. The drug was given a 6-month priority review, indicating that it was considered a major advance in treatment.

“Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer,” Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in a written statement on the approval.

A fully human monoclonal antibody with a unique mechanism of action, denosumab specifically targets the receptor activator of the nuclear factor kappa-B (RANK) ligand, the essential mediator of osteoclast fusion. The drug inhibits osteoclast formation, function, and survival, resulting in reduced bone resorption. The RANK ligand pathway was discovered by Amgen scientists in the mid-1990s, according to the company.

According to Amgen, bone metastases occur in 1.5 million cancer patients worldwide. They are most commonly seen in prostate, lung, and breast cancer. Denosumab was not approved for bone metastases related to multiple myeloma.

“A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating,” Amgen chairman and CEO Kevin Sharer said in a written statement. “We are pleased to offer this new advance to patients and their health care providers.”

The approval of denosumab was based on three phase III head-to-head trials comprising 5,700 patients that compared the drug with zoledronic acid (Zometa). The drug was superior to zoledronic acid in preventing skeletal-related events (SRE) in breast and prostate cancer. Some of that data was presented in June at the annual meeting of the American Society of Clinical Oncology. Denosumab was noninferior in preventing SREs in multiple myeloma and other solid tumors.

Adverse effects include hypocalcemia, fatigue, hypophosphatemia, and nausea. Osteonecrosis of the jaw can also occur.

The drug is given by subcutaneous injection once every 4 weeks. *

Because of the drug’s expense, Amgen is launching a new patient assistance program. The Xgeva First Step Coupon Program will provide assistance to eligible patients who need help meeting a deductible, copayment, or coinsurance. The first injection would be covered and subsequent injections would cost a maximum of $25.

Denosumab was approved in June to treat postmenopausal women with osteoporosis who are at high risk for fracture.

* CORRECTION, 11/19/2010: The original version of this article misstated the dosage frequency of denosumab (Xgeva). It is administered every 4 weeks as a subcutaneous injection. This version has been updated.