Osteoporosis Drug Seeking FDA Approval

Osteoporosis Drug Seeking FDA Approval
By: Madeline Ellis
Published: Thursday, 25 December 2008
Bone loss represents a major health threat for an estimated 44 million Americans, or 55 percent of the population 50 years of age and older, placing them at an increased risk for osteoporosis—a condition that leads to bone fragility and an increased susceptibility to fractures. A person with osteoporosis cannot feel their bones getting weaker, and may not know they have the disease until they break a bone from a major fall, or in serious cases, from as simple an action as sneezing. Women can lose up to one-fifth of their bone mass in the five to seven years after menopause, making them more susceptible to the disease. In fact, 80 percent of those affected by osteoporosis are women. The market for bone building drugs has been rather dominated by Merck and Company’s oral drug, Fosamax, but another, more convenient option may soon be available.

Amgen Inc. has filed for FDA approval of its investigational drug denosumab as a treatment for osteoporosis in post-menopausal women as well as treatment and prevention of bone loss in patients undergoing hormone therapy to treat either prostate or breast cancer. The application included data from six Phase 3 trials involving more than 11,000 patients, all showing denosumab’s ability “to increase bone density at all skeletal sites measured,” according to Roger Perimutter, executive president of Research and Development at Amgen. The two Phase 3 studies in the postmenopausal osteoporosis and prostate cancer settings with fracture endpoints also demonstrated the drugs’ ability to reduce fracture. In September, the company released results of a large clinical trial of denosumab that showed the drug reduced the risk of spine fractures in post-menopausal women suffering from osteoporosis by nearly 68 percent.

Denosumab is the first RANK Ligand inhibitor in late stage development. RANK Ligand is a protein that acts as the primary mediator of osteoclast (cells that break down bone) activity. Inhibiting RANK Ligand has been shown to significantly improve cortical bone (the protective outer shell around every bone in the body) and trabecular bone (spongy bone surrounded by the cortical layer) density, volume and strength.

Amgen is hopeful that denosumab’s convenience will lure patients who haven’t been successful with Fosamax or who have trouble remembering to take oral medications. Denosumab is designed to be injected under the skin twice a year with no restrictions, while Fosamax and similar oral drugs require patients to be sitting up when they take the pills and not to eat for two hours before and 30 minutes after taking the drug. Novartis’ once a year Reclast must be administered at an intravenous infusion clinic.

A spokeswoman for Amgen said the company expects to learn of the FDA’s decision within 60 to 75 days, when their review is concluded. Under a standard review, the FDA normally aims to make a decision within 10 months of the submission date. The California-based drug company says they will also submit a marketing application in the European Union, Switzerland, Canada and Australia for the same uses. In Europe, recent estimates have stated that approximately 3.8 million people have experienced bone fractures related to osteoporosis.

Amgen is not the only company awaiting marketing approval for an osteoporosis treatment. Pfizer’s drug Fablyn, also known as lasofoxifene, received a recommendation by an FDA advisory panel in September, but is still awaiting a formal decision. Fablyn belongs to a class of drugs known as selective estrogen receptor modulators (SERMs) and was developed to provide an effective treatment for postmenopausal osteoporosis—one that reduces the risk of both vertebral and non-vertebral fractures as well as addressing other postmenopausal conditions, including reduction in risk of breast cancer and treatment of vulvar and vaginal atrophy (VVA). Currently, no single medication addresses these needs together.