In re Rezulin Products Liability Litigation Lawsuit

In re Rezulin Products Liability Litigation

• Product: Rezulin (troglitazone), an oral type 2 diabetes treatment

• Manufacturer: Parke-Davis (Warner-Lambert; later Pfizer)

• Court: U.S. District Court for the Southern District of New York

• Judge: Lewis A. Kaplan

• Docket: MDL No. 1348

• Outcome: settlement (2009)

• MDL status: terminated

The product

Rezulin, the brand name for troglitazone, was a prescription medicine for adult type 2 diabetes. It belonged to the thiazolidinedione class, a group of agents designed to improve the body's response to insulin, and it was the first drug of that type to reach the market. The molecule was patented in 1983 and was developed in Japan by Sankyo; in the United States it was manufactured and marketed by Parke-Davis, the diabetes division of Warner-Lambert. The FDA approved the drug in January 1997, and it became a widely prescribed therapy for people with adult-onset diabetes.

The approval was not without controversy. The FDA medical officer originally assigned to the application had recommended against approval on the basis of concerns about liver and heart safety; after the sponsor's objections, the officer was removed from the review. After approval, the label was strengthened to warn of hepatotoxicity and to require periodic monitoring of liver enzymes.

The alleged harm

Some patients treated with Rezulin developed severe, idiosyncratic liver injury. In affected individuals the reaction progressed to acute liver failure; some required a liver transplant, and a number of patients died. The monitoring program built into the label — periodic blood tests of liver enzymes — proved unreliable as a shield: even closely monitored patients, including participants in a federal research study, suffered fatal liver failure, and FDA investigators concluded that monitoring did not prevent the worst outcomes. In March 2000, Warner-Lambert voluntarily withdrew Rezulin from the U.S. market. The drug had already been pulled from Britain in 1997 and from Japan shortly after the U.S. withdrawal. Pfizer, which had acquired Warner-Lambert in early 2000, inherited the withdrawn product and its liabilities.

The litigation

Claims by patients and their families alleging that Rezulin caused their liver injury were filed in both federal and state courts. The federal cases were centralized for coordinated pretrial proceedings in the U.S. District Court for the Southern District of New York as In re Rezulin Products Liability Litigation, MDL No. 1348, before Judge Lewis A. Kaplan (per the Second Circuit's 2005 opinion in the litigation).

The litigation centered on whether the drug caused the plaintiffs' liver damage, on the adequacy of the warnings on the label, and on the conduct of the approval and post-market review. Plaintiffs pointed to safety concerns raised before and after approval and to the failure of the mandated monitoring regimen. The defense emphasized that the injury was a rare, unpredictable idiosyncratic reaction in a drug that had treated many patients, and that the label and monitoring requirements had followed FDA guidance.

Resolution

The federal MDL ended in settlement in 2009. In that year, Pfizer resolved all but three of the roughly 35,000 Rezulin-related claims. The consolidated federal cases in New York were resolved in a separate settlement from the state-court suits, which were addressed in parallel proceedings. With the claims resolved, the MDL was terminated.

Rezulin remains one of the better-known examples of a widely used chronic-disease drug withdrawn after marketing because of liver toxicity, and of a mass-tort program in which the bulk of the federal cases were settled rather than tried to verdict.