Janssen Pharmaceutica, Inc. v. Bailey, No. 2002-CA-00736-SCT.

878 So.2d 31

JANSSEN PHARMACEUTICA, INC. and Johnson & Johnson v. Robert BAILEY, Rosie Lee Bell, Barbara Bishop, Connie Coleman, Martha Evans, Macy B. Johnston, by and through her Natural Parents and Next Friends, Milton Johnston, Tracy Johnston, Maurice Landers, Elsie Queen, Janis White and Mary Williams.

No. 2002-CA-00736-SCT.

Supreme Court of Mississippi.

May 13, 2004.

As Modified on Denial of Rehearing August 5, 2004.

Donna Brown Jacobs, Christy D. Jones, Kari Louise Foster, John C. Henegan, Robert L. Johnson, III, Walter Estes Dellinger, Richard B. Goetz, Charles C. Lifland, Anita K. Modak-Truran, Jackson, attorneys for appellants.

James D. Shannon, Elise Berry Munn, Kelley Mitchell Berry, Hazlehurst, Lonnie D. Bailey, James E. Upshaw, Greenwood, Mark C. Carroll, Jackson, Renee C. Harrison, Hazlehurst, Edward Blackmon, Jr., Canton, T. Mark Sledge, James B. Grenfell, Jackson, attorneys for appellees.

EN BANC.

CARLSON, Justice, for the Court.

¶ 1. This case involves the prescription medication Propulsid, which is used to treat gastroesophageal reflux disease. On July 6, 2000, 155 plaintiffs filed this action against Janssen Pharmaceutica and Johnson & Johnson (hereinafter collectively "Janssen") in Jefferson County Circuit Court, alleging injuries caused by Propulsid. The plaintiffs also sued local pharmacies, McDaniel Pharmacy and Bankston Rexall, but the trial court directed verdicts in their favor when the plaintiffs failed to introduce evidence against the pharmacies at trial. The Appellees in this case (hereinafter "Plaintiffs") include ten of those original 155 plaintiffs who were designated as a "trial group" by Plaintiffs' counsel.

¶ 2. Venue was transferred from Jefferson County to Claiborne County, and trial commenced on September 4, 2001, with the Hon. Lamar Pickard, presiding. The Plaintiffs asserted two claims: (1) that defendants had inadequately warned of Propulsid's potential side effects, and (2) that defendants had negligently misrepresented Propulsid's benefits. At the close of the trial, the trial court granted Janssen a directed verdict on the misrepresentation claims because the Plaintiffs offered no proof that they nor they physicians relied on any misrepresentation made by Janssen. The jury awarded compensatory damages of $10 million per plaintiff ($100 million total). The trial court directed a verdict for Janssen on the Plaintiffs' punitive damages claims. Janssen's post-trial motion for a remittitur was granted, and the trial court reduced the total amount of damages to $48 million. On March 28, 2002, the trial court entered a Final Judgment pursuant to Miss. R. Civ. P. 54(b). Janssen has now perfected this appeal before this Court. Because of our recent decision in Janssen Pharmaceutica, Inc., v. Armond, 866 So.2d 1092 (Miss.2004), our mandated course of action today is clear.¹

FACTS AND PROCEEDINGS IN THE TRIAL COURT

Background:

¶ 3. Propulsid is a prescription medication used to treat gastroesophageal reflux disease (GERD), the abnormal backflow of stomach acids into the esophagus. GERD's main symptom is heartburn caused by acid irritating the esophagus, but its sufferers often experience chest pain, cough and nocturnal asthma attacks. Chronic GERD can cause esophageal ulcers, scarring of the esophageal lining and constriction of the esophageal pathway. GERD may also damage the vocal chords, lungs and even the teeth. Left untreated, GERD can lead to esophageal cancer in both children and adults.

¶ 4. Propulsid, which is also known by its chemical name "cisapride", is a prokinetic² agent causing it to work differently from other treatments for GERD. While other medications only treat acid and do not block backflow, Propulsid, a motility drug, works by tightening the opening between the esophagus and the stomach increasing the rate at which both the esophagus and stomach move food through the body.

¶ 5. Janssen Pharmaceutica, Inc., a New Jersey and Belgium-based drug company owned by the New Jersey-based Johnson & Johnson, developed Propulsid in Europe in the 1980s. In 1988, after eight years of research, European regulators approved Propulsid as a prescription medication for GERD and other motility disorders in both adults and children.

¶ 6. Propulsid first became available in the United States in 1983 in an investigational program approved by the U.S. Food and Drug Administration (FDA), which exclusively regulates the availability of prescription drugs under the Food, Drug and Cosmetic Act, 21 U.S.C. §§ 301 et seq. In July 1993, after more clinical trials, the FDA approved Propulsid as a "safe and effective" treatment for the symptomatic relief of nocturnal heartburn due to GERD in adults. See id. §§ 355(d), 393(b)(2)(B).

¶ 7. By law, the labeling of every prescription drug must include a package insert listing known side effects. 21 C.F.R. §§ 201.56-201.57 (2002). The FDA must approve the content of such inserts, which communicate to prescribing physicians the essential information about the medication's benefits and risks. When new side effects come to light, the FDA may require the manufacturer to revise the package inserts. Id. § 201.57(e). For significant revisions, the FDA may also require manufactures to disseminate "Dear Doctor" letters giving prompt and particularized notice of the new information. 21 U.S.C. § 355(e); 21 C.F.R. § 200.5. ¶ 8. Propulsid's initial U.S. package insert was issued in July 1993. After reviewing a 1992 report issued by two clinicians in the British Medical Journal which stated that seven patients under treatment with Propulsid had experienced tachycardia³ which ended when the patients discontinued the drug but in three instances reappeared when they restarted the drug, the FDA concluded that although the risk of adverse heart events appeared "very low", Janssen was required to disclose these events in their initial U.S. labeling. The "ADVERSE REACTIONS" section of the 1993 package insert accordingly included a statement disclosing the known risk.

¶ 9. In 1994 Janssen received reports that two patients taking Propulsid in conjunction with high doses of the anti-fungal medicine ketoconazole had experienced a rare but potentially serious heart arrhythmia known as "torsades de pointes."⁴ After reporting these events to the FDA, Janssen initiated a study of possible interactions between Propulsid and ketoconazole. The study confirmed that ketoconazole inhibited production of the liver enzymes that break down and eliminate Propulsid from the body, increasing the drug's normal concentration in the body as much as eight-fold. The study also suggested that in some patients, this interaction could lengthen the patient's QT-interval, or the time it takes the heart to reset itself between beats as measured on an EKG.

¶ 10. After reviewing this information and other post-marketing reports of adverse cardiac events with the FDA, Janssen issued a new package insert and a "Dear Doctor" letter in February 1995 which warned that in rare cases, patients taking Propulsid had experienced "serious cardiac arrhythmias, including ventricular arrhythmias and torsades de pointes associated with QT prolongation." The new FDA-approved labeling contraindicated use of Propulsid with ketoconazole and other drugs that Janssen believed would likely exhibit similar interactions.

¶ 11. The "WARNINGS" section and a revised "ADVERSE REACTIONS" section noted that "most" of the reported events had involved patients who took "multiple other medications and had preexisting cardiac disease or risk factors for arrhythmias." The "WARNINGS" section also stated that some of the events had involved patients with no known cardiac histories. A revised "PRECAUTIONS" section advised that physicians should carefully weigh the benefits against the risks before prescribing Propulsid to patients with preexisting risk factors for QT prolongation.

¶ 12. In October 1995, Janssen again revised the package insert to expand the list of potentially interactive drugs. Janssen also reported in the "WARNINGS" and "ADVERSE REACTIONS" sections that some rare cardiac events associated with Propulsid had been fatal. This warning was emphasized in a separate "Boxed Warning" printed at the top of the package insert. Janssen also mailed out "Dear Doctor" letters highlighting the revised and expanded warnings.

¶ 13. In March 1998, Janssen and the FDA again reviewed recent adverse reports about Propulsid, and it was agreed that Janssen would issue a new package insert which reinforced and expanded previous warnings. The new FDA-approved labeling, which was issued in June 1998, carried an expanded "Boxed Warning" that contraindicated Propulsid, not only for patients taking potentially interactive drugs, but also for patients otherwise predisposed to QT prolongation, taking other QT prolonging drugs or having conditions potentially predisposing them to arrhythmias. The package insert similarly expanded the warnings found in the "CONTRAINDICATIONS," "WARNINGS" and "PRECAUTIONS" sections and further advised that because of the risk of serious ventricular arrhythmias, physicians should administer Propulsid only after other therapies had failed. These changes were also highlighted in a "Dear Doctor" letter mailed to over 800,000 physicians and pharmacists.

¶ 14. In June 1999, Janssen issued another "Dear Doctor" letter revising the package insert to contraindicate Propulsid for patients with family histories of congenital long QT syndrome and those with clinically significant bradycardia.⁵ At the FDA's request, another "Dear Doctor" letter was issued in January 2000 which revised the package insert advising physicians not to prescribe Propulsid to any patient whose QT interval exceeded 450 milliseconds.

¶ 15. In March 2000 after further consultation with the FDA, Janssen announced its decision to make Propulsid available only through an investigational limited access program. Because many...