Fosamax: 2d bellwether case dismissed

Osteonecrosis of the jaw is a widely reported phenomenon among patients taking bisphosphonates - the class of drugs to which Fosamax belongs.

In 2005 Merck, with FDA approval, changed its label, adding this Precaution:

Dental

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported in patients taking bisphosphonates. Most reported cases of bisphosphonate-associated osteonecrosis have been in cancer patients treated with intravenous bisphosphonates, but some have occurred in patients with postmenopausal osteoporosis.

Known risk factors for osteonecrosis include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), poor oral hygiene, and co-morbid disorders (e.g., pre-existing dental disease, anemia, coagulopathy, infection).

Patients who develop osteonecrosis of the jaw (ONJ) while on bisphosphonate therapy should receive care by an oral surgeon. Dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk for

ONJ. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

The American Association of Oral and Maxillofacial Surgeons, in a Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaws Approved by the Board of Trustees September 25, 2006 expressed the conviction of practitioners that the hazard was well established for some patients. In legal argot this is evidence in favor of "general causation" - that the drug can have the toxic effect in at least some patients.

The first of the 950 Fosamax cases to be selected for trial in the consolidated Multi District Litigation was declared a mistrial because of a bitter interpersonal conflict within the jury. The second - Bessie Flemings v. Merck - pitted a 73 year old cancer patient against Merck. U.S. District Judge John Keenan - manager of the cases - dismissed Fleming's case after a Daubert motion narrowed the class of cases which he deemed were sufficiently supported to go to a jury.

The court was dismissive of the quality of the medical evidence. Keenan found that plaintiff's dentists had not presented adequately reasoned opinions linking Fosamax to Fleming's affliction - one to which cancer patients are particularly prone. The treating physicians' `subjective belief' was inadequately supported by reasoning and could not establish the necessary individual causal link ["specific causation"], Keenan ruled.

Particularly sensitive patients are very risky for plaintiffs. While the vulnerability of the plaintiff is appealing, the presence of a strong pre-disposition is very dangerous for proof of the drug's causal role. Weak dose-response evidence often proves fatal unless the biological mechanism strongly implicates the drug. That was fatal to Flemings' claim - and is an ill omen for the upcoming plaintiffs. Judge Keenan finished the job he began in July 2009. He ruled then in Daubert motions that plaintiffs had no proof sufficient to establish that stopping Fosamax led to any improvement in patients with active osteonecrosis.

Plaintiff does not provide the Court any scientific literature or studies that would support Dr. Rose’s theory of causation. Through the course of this multi-district litigation, other experts have opined based on scientifically valid methodologies that Fosamax can cause ONJ. However, nowhere in its opposition to Defendant’s motion for summary judgment, or in the exhibits attached thereto, does Plaintiff provide the Court information regarding Dr. Rose’s theory — that a patient’s ONJ would heal soon after she stopped taking Fosamax only if in fact the injury was caused by the drug.5

5 The Court observed in its ruling on the parties’ Daubert motions that the Plaintiffs’ Steering Committee and its experts “did not defend the reliability” of a similar theory — that a “drug holiday” before dental surgery reduces the risk of developing ONJ. In re Fosamax Prods. Liab. Litig., No. 06 MD 1789, 2009 WL 2222910, at *31 (S.D.N.Y. July 27, 2009). The Court therefore granted Merck’s motion to preclude testimony that “cessation of Fosamax treatment is appropriate before major dental surgery.” Id.

Complete opinion dismissing Bessie Flemings v. Merck & Co., Inc., November 26, 2009, SDNY, 1:06-cv-7631 (JFK)

Resources:

Medline Plus: Fosamax (alendronate) page [National Institutes of Health]

FDA Postmarket safety page

Journal of Oral & Maxillofacial Surgey