Last month, the Third Circuit issued another appellate opinion in the long-gestating In re Fosamax litigation (3d Cir Sept. 20, 2024, – F. 4th, 2024 WL 4247311). The litigation, now well into its second decade, involves claims that use of the bisphosphonate drug Fosamax caused atypical femoral fractures (AFF). In 2013, a District Court of New Jersey court found that FDA's Complete Response Letter (CRL) in 2009 rejecting a proposed label change to warn of the risk of “stress fractures” preempted plaintiffs' state-law claims. On appeal to the Third Circuit, the appellate court reversed - finding that under Wyeth the District Court did not apply the “clear evidence” standard to its inquiry. On appeal to the Supreme Court, the Third Circuit's decision was vacated. Clarifying its holding in Wyeth, the Court found in Albrecht that the “clear evidence” standard was a question of law for the trial court to decide based on a two-pronged test focused on whether the relevant state and federal laws "irreconcilably conflict."

Upon remand to the District Court of New Jersey, the trial court again found preemption - determining that the manufacturer of Fosamax "fully informed" the FDA of its reasoning to add a “stress fracture” warning and FDA's CRL said “it would not approve changing the Fosamax label.” The trial court went on the analyze the context of the CRL, finding that when considering the context of the CRL in light of corresponding informal communications, the rejection of the warning was because FDA doubted the causal association of AFFs and bisphosphonate use and not because the term “stress fracture” was used.  

However, in its most recent ruling, the Third Circuit again reversed. The appellate court found that the trial court erred in concluding - based on the record before it - that the FDA would have rejected any and all labels that would have satisfied state law. Explaining its reasoning, the court found that a CRL could act to preempt state law claims, but in this context the letter did not clearly and equivocally set forth that the proposed warning was rejected because FDA would never add a warning about AFFs to a Fosamax label as the letter could also be read that FDA would have potentially added a warning with different language. Given the “presumption against pre-emption” outlined in Albrecht and the CRL's failure to “clearly reject[] . . . [the] label in a manner that made it evident that no label” would be approved, the state law claims were not found to be preempted and the trial court's ruling was reversed. The appellate court acknowledged the difficult position its ruling put the defendant in, stating "[w]e are not unsympathetic to the pressures . . . faced from the competing demands of a possible state law requirement and FDA action, but there is no escaping the consequences of Albrecht."   

More than "competing demands," the decision puts registrants of FDA-approved medications between the proverbial rock and a hard place. Even in a situation where a company seemingly does everything the plaintiffs' bar suggests they should have done - up to and including adding a warning regarding the injury plaintiffs have sued the company over - and that warning is rejected, a company may still be held liable for failure to warn. The In re Fosamax decision will likely be appealed to the Supreme Court for further clarification but in the meantime, companies hoping to change the labeling to FDA-approved products should request clarification from FDA when warnings are rejected that no warning regarding the potential adverse effect will be accepted by the agency - not just the warning provided by the registrant.