In re Fosamax (Alendronate Sodium), No. 11-5304, 08-08; U.S. District Court (DNJ); opinion by Pisano, U.S.D.J.; filed June 27, 2013. DDS No. 36-7-xxxx [17 pp.]

Fosamax (Alendronate Sodium) is approved by the U.S. Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis.

In June 2008, the FDA contacted defendant Merck, Sharp, & Dohme Corp and other bisphosphonate manufacturers and requested any investigations they conducted regarding the occurrence of atypical femur fractures (AFFs) with bisphosphonate use, any investigational plans, and all hip and femoral fracture case reports they received. Defendant responded, sending summary tables of clinical and postmarketing data, clinical Council for International Organizations of Medical Sciences reports, and postmarketing CIOMS reports. The FDA's review of the received data did not show an increase in the risk of atypical subtrochanteric femur fractures in women using these medications.

In September 2008, defendant submitted a prior approval supplement (PAS) to the FDA proposing to add language to both the precautions and adverse reactions/post-marketing experience sections of its label to describe low-energy subtochanteric femoral fractures.

Bernadette Glynn had been prescribed Fosamax after being diagnosed with osteopenia–osteoporosis in 2002. She took Fosamax until April 2009, when she fractured her right femur.

One month after her fracture, the FDA advised defendant that it was recommending that it add low energy femoral shaft and subtochanteric fractures to the adverse reactions/postmarketing experience section of its label but that it was not approving the proposed change to the precautions section. Defendant's proposed change to the adverse reactions/postmarketing experience section was submitted in July 2009 and approved in March 2010.

In October 2010, the FDA issued a drug safety communication requiring bisphosphonate manufacturers to add information on AFFs to the precautions section of the drug labels and a new limitations on use statement in the indications and usage section because AFFs may be related to long-term bisphosphonate use. Defendant has made these changes.

Glynn and her husband, Richard, allege Fosamax caused Bernadette's femur fracture and that defendant failed to warn physicians about Fosamax and AFFs. Defendant argues that plaintiffs' claims are pre-empted because the FDA rejected its proposed label change and this is clear evidence that the FDA would not have approved a stronger warning to the precautions section of the label.

The court heard oral argument on the federal pre-emption issue and reserved decision until a trial record had been established. A jury returned a verdict for defendant, finding that plaintiff did not prove by a preponderance of the evidence that she experienced an AFF.

Presently pending are defendant's motions for summary judgment based on federal pre-emption and for judgment as a matter of law pursuant to Rules 50(a) and 50(b).

Held: Pre-emption is warranted because there is clear evidence that the FDA would not have approved a change to the precautions section of the Fosamax label prior to Mrs. Glynn's fracture.

Federal law pre-empts state law in three ways: (1) express pre-emption; (2) field pre-emption, and (3) conflict pre-emption. The court says this case concerns conflict pre-emption because defendant argues that it was impossible to comply with the state law duty to warn and the FDA's regulations since the FDA rejected a proposed warning about low-energy femur fractures prior to Mrs. Glynn's fracture.

The court finds that pre-emption is warranted because the FDA's rejection of defendant's proposal to change the precautions section of the label constitutes clear evidence that it would not have approved a label change to the precautions section of the label prior to the injury at issue.

The court says the evidence presented at trial supports this conclusion, where one of plaintiffs' experts who was "central" to their pre-emption analysis, and one of defendant's experts both testified that the FDA "rejected" a precaution to the Fosamax label. Further, defendant's expert testified that although the FDA had the authority to ask defendant to submit "alternative precautionary language" if it was "still contemplating that they might accept a precaution," it did not do so, thereby indicating that it would not accept a label change to the precautions section of the Fosamax label at that time.

The court finds that plaintiffs did not present any evidence to refute pre-emption. First, they did not offer any evidence that defendant's PAS was rejected due to language, specifically, the use of "stress fracture" instead of "AFF," or that the FDA would have approved a properly worded label change. Second, plaintiffs did not offer any evidence that defendant could have submitted a changes-being-effected supplement to change the precautions section of the Fosamax label, which would have given MSD the ability to change the label without FDA approval. Like a PAS, the proposed change must be based on reasonable evidence of an association between a hazard and the drug at issue. Since the FDA rejected defendant's PAS, it would not have approved a CBE seeking to add the same language to the label that it just rejected in the PAS, and any changes defendant made using the CBE supplement would cause the drug to be misbranded. Third, plaintiffs did not show that defendant failed to provide all the information it had on femur fractures to the FDA or failed to warn the FDA as soon as there was reasonable evidence of a causal association between Fosamax and AFFs.

Therefore, the court concludes that pre-emption is warranted.