FDA Approves Yearly Zoledronic Acid for Men

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS