Supreme Court Grants Small Win for Merck’s Osteoporosis Drug Fosamax

In a unanimous decision, the U.S. Supreme Court threw out a lower court’s ruling that Merck failed to warn patients of significant fracture risk associated with its osteoporosis drug Fosamax. The justices said that a judge—not a jury—should decide whether hundreds of lawsuits against Merck should move forward. The more than 500 patients that wish to sue the pharmaceutical company sustained unusual thigh fractures between 1999 and 2010 after taking Fosamax.

Fosamax received approval from the Food and Drug Administration (FDA) in 1995, at which time the correlation between the medication and thigh bone fracture was not as well established, although a possible connection was observed as early as 1990 or 1991 when the drug was in its testing phases. Merck brought up this possibility when applying for FDA approval for Fosamax, but the FDA did not require Merck to include this warning at the time.

Overtime, however, more evidence came to light linking Fosamax to thigh bone fracture. The Supreme Court’s opinion states: “For example, Merck received a report from a doctor who said that hospital staff had begun calling atypical femoral fractures the ‘Fosamax Fracture’ because ‘100% of patients in his practice who have experienced femoral fractures (without being hit by a taxicab), were taking Fosamax . . . for over 5 years.’ Merck performed a statistical analysis of Fosamax adverse event reports, concluding that these reports revealed a statistically significant incidence of femur fractures. And about the same time, Merck began to see numerous scholarly articles and case studies documenting possible connections between long-term Fosamax use and atypical femoral fractures.”

In 2008, Merck requested that a warning be added to both the adverse reactions and precautions sections of Fosamax’s label—”In particular, Merck proposed adding a reference to ‘low-energy femoral shaft fracture’ in the Adverse Reactions section, and cross-referencing a longer discussion in the Precautions section that focused on the risk of stress fractures associated with Fosamax,” the Court’s opinion explains. The FDA granted approval for the adverse reactions addition but not the warning for “stress fractures,” saying the company’s “justification” was “inadequate” because, quoting the FDA, “[i]dentification of ‘stress fractures’ may not be clearly related to the atypical subtrochanteric fractures that have been reported in the literature.” The FDA invited Merck to resubmit its request with different language, but Merck went ahead with the approved addition.

In 2011, the FDA added an “atypical femoral fractures” warning to Fosamax’s label based on its own findings. Once again, Merck suggested using the term “stress fractures,” which the FDA rejected for a second time, claiming this language was not strong enough to convey the severity of the risk.

Fosamax: Doses, Indications, Adverse Effects

Fosamax is a bisphosphonate indicated to treat or prevent osteoporosis in postmenopausal women, increase bone mass in men with the disease, treat osteoporosis patients also using corticosteroid medicines, and treat Paget’s disease of the bone. The FDA has not determined the optimal duration of Fosamax treatment. The current recommended doses are:

  • Treatment of osteoporosis in postmenopausal women and men: 10 mg/day or 70 mg (tablet or oral solution)/week
  • Prevention of osteoporosis in postmenopausal women: 5 mg/day or 35 mg/week
  • Glucocorticoid-induced osteoporosis: 5 mg/day, or 10 mg/day in postmenopausal women not receiving estrogen
  • Paget’s disease: 40 mg/day for six months

The most common side effects include abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain, and nausea. In addition to atypical femur fractures, the FDA also warns of:

  • Severe irritation of upper gastrointestinal mucosa
  • Worsening hypocalcemia
  • Severe bone, joint, or muscle pain
  • Osteonecrosis of the jaw

Sources: Reuters, Supreme Court, FDA: Fosamax; Medication Guide