No-preemption ruling spurs Zyprexa cases forward.

Although Eli Lilly & Co. has settled more than 29,000 of the 30,000 lawsuits brought by plaintiffs who allege that its antipsychotic drug Zyprexa caused excessive weigh t gain, hyperglycenua, and diabetes, the remaining cases are heading to trial following a federal district court's finding in the multidistrict litigation (MDL) that those plaintiffs' state law failure-to-warn claims are not preempted.

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In rejecting Lilly's argument that a new preamble in the FDA's drug-labeling rules preempts state tort claims, Senior District Court Judge Jack Weinstein of the Eastern District of New York noted that "the regulation of public health is an area traditionally occupied by the states, supporting a presumption against preemption." He found that Congress had not clearly stated an intent to preempt these claims. (In re Zyprexa Prods. Liab. Litig., 2007 WL 1678078 (E.D.N.Y. June 11, 2007).)

"The FDA cannot be allowed to usher in such a sweeping change in substantive law through the back door," Weinstein wrote.

The ruling was a significant blow to preemption proponents. Howard Nations of Houston, cochair of the plaintiffs' steering committee in the MDL, said, "Judge Weinstein, exhibiting his customary level of judicial wisdom, rejects the FDA's thinly veiled political efforts to usurp congressional power by creating preemption in its preamble. Through the preamble, the FDA seeks to afford another level of protection to the pharmaceutical companies that the FDA is supposed to regulate. Judge Weinstein's ruling properly rejects the FDA's attempted power grab by recognizing the need for congressional approval before preemption can be imposed."

In denying Lilly's motion for summary judgment, Weinstein found that questions of fact exist concerning whether the company's warning to physicians was adequate--in light of the company's marketing efforts--to convey the drug's risks. The ruling has set the stage for the first Zyprexa cases to go to trial early next year.

Zyprexa is one of the class of drugs known as atypical antipsychotics, which includes AstraZeneca's Seroquel, and Janssen, L.R, and Johnson & Johnson's Risperdal. These drugs have become the subject of litigation ranging from products liability failure-to-warn cases to shareholder class actions, RICO claims, and state Medicare actions.

Currently the fourth-largest group of medications prescribed in the United States, atypical antipsychotics are approved for the treatment of symptoms of schizophrenia and the acute manic episodes associated with bipolar disorder in adults and for symptoms of irritability associated with autism in children.

Doctors also routinely prescribe atypical antipsychotics off-label for conditions not approved by the FDA, including depression, dementia-related behavior problems, personality disorders, Tourette's syndrome, obsessive-compulsive disorder, and posttraumatic stress disorder, despite what critics say is a lack of strong evidence that they are effective in treating these conditions.

The FDA approved the first atypical-antipsychotic formulations in the mid1990s. By May 2000, it began to analyze postmarket reports that users had experienced adverse side effects, including diabetes and hyperglycemia. In September 2003, the agency ordered that package inserts for the drugs carry a new warning about the risks of weight gain and diabetes.

Most of the failure-to-warn cases against the manufacturers involve plaintiffs who took the drugs before September 2003. For example, in the Zyprexa MDL, plaintiffs allege that the drug caused them adverse effects; that the company misled them and their doctors about the likelihood of these effects; and that they would not have taken the drug if they or their doctors had been aware of the risks.

Lilly contends that these claims are without merit but that it was in the best interests of the company, patients, and prescribing physicians to enter into the settlement agreements.

More litigation action

In Florida, the proceedings in a Seroquel MDL against AstraZeneca are heating up. The litigation involves about 7,000 plaintiffs. Earlier this year, the court severed the plaintiffs' cases, requiring separate filings. (In re Seroquel Prods. Liab. Litig., 2007 WL 737589 (M.D. Fla. Mar. 7, 2007).) The court also has imposed a discovery order requiring that depositions be completed at the rate of 30 cases per month.

Paul Pennock of New York City, co-lead counsel in the MDL, said the deposition schedule is posing a challenge for the attorneys involved.

"That is a particularly tight timetable on discovery, as you have 30 cases [per month], and every one has depositions of the plaintiff, the treating physician, the prescribing physician, and the [drug company's] sales rep" at a minimum, he said. "The judge essentially wants every case done by the end of the summer of 2008."

Pennock also noted that, after the court expressed frustration with Astra-Zeneca's refusal to mediate the cases, the company said that it would consider mediation next year.

Several thousand personal injury cases filed in state courts in New Jersey against the manufacturers of Risperdal, Seroquel, and Zyprexa have been centralized in a single mass-tort proceeding. The suits, which headed into discovery over the summer, involve injuries resulting from tile off-label prescribing of the drugs, and many of the plaintiffs are children. (In re Risperdal/Seroquel/Zyprexa Litig., No. 274 (NJ., Middlesex Co. Super. Sept. 28, 2006).)

Philadelphia attorneys Stephen Sheller and James Pepper, who represent some of the New Jersey plaintiffs, believe the increasing pediatric use of atypical antipsychotics is cause for concern. One of their clients, a teenage boy who was prescribed Risperdal off-label for generalized anxiety disorder, experienced Risperdal-induced akathisia (an intense inner restlessness or constant urge to move) and elevated levels of the hormone prolactin, which caused him to develop breasts so large that he required a double mastectomy. He also developed hyperglycemia and diabetes.

"The pediatric problems are particularly egregious," said Pepper. "These are very, very powerful drugs, and they are not necessarily better in terms of efficacy" than older treatments.

Lilly also faces a number of shareholder class actions involving allegations that the company and some of its officers and directors made false and misleading statements about Zyprexa, failed to warn the public of serious health risks associated with it, and actively marketed it for off-label uses. The plaintiffs claim that these activities exposed Lilly to regulatory penalties and legal actions and resulted in a dramatic drop in the value of its stock and the company's overall market value.

Meanwhile, several state attorneys general have sued Lilly seeking reimbursement for money paid by their state Medicaid programs for Zyprexa, which--at more than $300 for a monthly prescription--constitutes the single biggest drug cost for many state Medicaid budgets.

Montana's lawsuit, for example, claims that Lilly gave kickbacks to doctors, improperly promoted Zyprexa to nursing homes as a sedative, and fraudulently created a 280-person sales force to promote the drug exclusively tot off-label uses, specifically in long-term care facilities. The state seeks reimbursement for prescription costs and the costs of medical care for patients harmed by the drug. (Montana v. Eli Lilly & Co., No. ADV-2007-188 (Mont., Lewis & Clark Co. Dist. filed Mar. 7, 2007).)

Moreover, RICO class actions have been brought against Lilly, AstraZeneca, Janssen, and Johnson & Johnson by union insurance plans, pension funds, and other private health insurers, who claim that the companies engaged in illegal schemes to market and promote their antipsychotic drugs for off-label uses.

The RICO claims against Lilly have been combined with the MDL in New York. According to Lauren Barnes of Boston, one of the lawyers for the insurer plaintiffs, Lilly specifically encouraged many of the off-label uses "in our most vulnerable populations--children and the elderly. Lilly accomplished this over-promotion (and the massive sales of a drug approved for use in only a tiny slice of the population) by purposefully permeating, manipulating, and corrupting every channel through which physicians receive information about prescription pharmaceuticals."

Although Lilly sought dismissal of the RICO claims, Weinstein again ruled against the company, denying its motion for summary judgment. (In re Zyprexa Prods. Liab. Litig., 2007 WE 1851161 (E.D.N.Y. June 28, 2007).)

"Allowing this and like suits to proceed may or may not increase the cost of pharmaceuticals and the efficacy of medical treatment in this country," Weinstein wrote. "It does, however, furnish backstop protection against under-regulated potentially dangerous activity by a market where caveat emptor largely rules."