Courts will determine fate of generic painkiller

The painkiller OxyContin is at the center of several lawsuits that claim its manufacturer, Purdue Pharma, blocked generic competition and misled federal authorities, costing Americans and health insurers billions of dollars.

The lawsuits stem from patent litigation between Purdue Pharma and Endo Pharmaceuticals Holdings, which had filed an ANDA to introduce a generic version of OxyContin (oxycodone HCl controlled-release). In January 2004, Judge Sidney Stein found that while Endo had infringed on three of Purdue's patents, the patents were unenforceable because Purdue deliberately misled federal authorities at the U.S. Patent and Trade Office.

Following Judge Stein's decision, a class-action lawsuit was brought against Purdue Pharma by a number of consumer groups, representing millions of plaintiffs. It claimed that the Stamford-based company reaped billions of dollars in unlawful profit from OxyContin by preventing generic alternatives from reaching the market. The suit alleges that Purdue Pharma violated federal and state antitrust laws by misleading the patent office in claiming that Oxycontin was effective at very low doses when there were no clinical data to support the claim at the time the patent application was filed.

"From what we can see, the Patent and Trade Office did its usual appropriate due diligence," said Thomas Sobol, an attorney with Hagens Berman, representing the plaintiffs through the group Prescription Access Litigation on behalf of Connecticut Citizen Action Group and Health Care for All. "The question is really whether Purdue disclosed what it was required to disclose and whether it misled federal authorities."

A second class-action lawsuit was filed in February, and attorneys general from Connecticut and other states may consider pursuing antitrust violations in the near future. "We will investigate aggressively and vigorously possible legal action seeking antitrust remedies, and we've already begun organizing other states to do so with us," Connecticut Attorney General Richard Blumenthal told the New York Times.

Purdue Pharma countered by denying the allegations and filing an appeal to overturn the judge's ruling. "We believe our patents for OxyContin should be held valid and enforceable. As a consequence, we will move expeditiously in the district court and in the court of appeals to vindicate our position," said Howard Udell, Purdue Pharma's executive VP and chief legal officer, in a statement.

Purdue Pharma stated that in cases where district courts have made findings of inequitable conduct, the court of appeals for the federal district has either reversed or vacated those rulings in more than 70% of the cases within the past year.

Commenting on the case in an editorial in Pharmaceutical Law and Industry Report, Bruce Lehman, who served as Assistant Secretary of Commerce and U.S. commissioner of Patents and Trademarks for more than five years, expects the decision to be reversed on appeal. According to Lehman, Judge Stein misinterpreted the patent office rules "because scientists who conceive of new medicines inevitably 'invent' them before clinical trials can take place. In the case of pharmaceutical inventions, patent applications are nearly always filed as soon as possible after the inventor had his breakthrough insight and before clinical testing can take place."

Lehman concluded that Connecticut Attorney General Blumenthal and others "should be wary about taking any actions based on the flawed trial court opinion."

Center of attention

Purdue Pharma is no stranger to controversy. Since its opioid agonist was approved by the Food & Drug Administration in December 1995, Purdue Pharma has wrestled with numerous lawsuits. OxyContin has been the subject of government hearings and special news reports about its illegal use among abusers, who often chew the tablets, crush them and snort the powder, or dissolve them in water and inject the drug for a fast high. Like other addicts, OxyContin abusers are known to commit crimes and theft to sustain their habits; forgery or alteration of prescriptions is also commonplace.

By the late 1990s, abuse of OxyContin, which is twice as potent as morphine, was out of control in Appalachia, where it soon became known as "hillbilly heroin." Several deaths resulted from OxyContin abuse in states like Kentucky, Ohio, Virginia, and West Virginia, but the exact number is unknown. Some of the deaths have been associated with OxyContin as well as other pain relievers, medications for anxiety and sleep disorders, marijuana, and alcohol.

Although OxyContin is classified as a Schedule II controlled substance, the FDA never predicted its widespread misuse. In fact, FDA officials testified before the U.S. Senate Committee on Health, Education, Labor, and Pensions in 2002 that the agency believed the controlled-release characteristics of OxyContin would result in less abuse because the drug would be absorbed more slowly without an immediate high that would promote abuse.

"At the time of OxyContin's approval, the FDA was aware that crushing the controlled-release tablet followed by intravenous injection of the tablet's contents could result in a lethal overdose." So testified John Jenkins, M.D., director, Office of New Drugs, at the FDA's Center for Drug Evaluation and Research. "A warning against such practice was included in the approved labeling. The FDA did not anticipate, however, nor did anyone suggest, that crushing the controlled-release capsule followed by intravenous injection or snorting would become widespread and lead to a high level of abuse."

In July 2001, Purdue Pharma, working in cooperation with the FDA, had updated the warnings and precautions sections of the label and added a "black box" warning to notify patients and physicians of the potential consequences of misusing the drug.

Legal maneuvers

While Purdue Pharma faces numerous lawsuits associated with OxyContin abuse, the patent litigation started in 2000 when Endo filed an ANDA to market generic copies of OxyContin. Immediately, Purdue Pharma countersued that Endo was infringing upon several of its patents. The case was finally heard in Manhattan courts and concluded in favor of Endo, paving the way for generic versions of OxyContin. Two other drug companies, Teva Pharmaceuticals and Impax Laboratories, are awaiting final clearance from the FDA to introduce their generic versions.

In a preemptive move, Purdue Pharma filed a petition with the FDA to withhold final approval of generic forms of OxyContin until the generic companies implemented a risk-management program to minimize misuse and abuse of the drug.

"Since any generic long-acting oxycodone product will have the same abuse potential as OxyContin, we feel it is necessary for generic manufacturers to implement risk-management programs that match the elements and rigor of our program," said David Haddox, M.D., VP of health policy for Purdue Pharma. Purdue Pharma officials noted that the FDA and Drug Enforcement Administration expressed concerns about generic oxycodone products entering the market without adequate risk-management programs in place.

Soon after Purdue Pharma began selling OxyContin in the United States and realized the growing misuse of the drug, the company took action to educate healthcare professionals about proper pain management and the safe use of OxyContin. Education of law enforcement officials and the general public was also part of the program. To combat forgery of OxyContin Rxs, Purdue Pharma developed tamper-resistant prescription pads printed on special security paper with anti-counterfeiting technology that about 15,000 doctors use to write prescriptions for controlled substances.

In 2002, the company also established a new initiative, designed to collect quantitative and qualitative information, to study the prevalence of abuse and addiction of controlled drugs, and to develop more effective prevention and intervention efforts.

Endo has agreed to voluntarily develop a risk-management program to avoid wrongful use of the drug, commented Bill Newbould, VP of corporate communications for Endo Pharmaceuticals, based in Chadds Ford, Pa. In July 2002, the FDA granted Endo tentative approval for the company's ANDA for all four strengths (10, 20, 40, and 80 mg) of OxyContin. The company expects to have 180 days of marketing exclusivity for three of the four dosages. Teva filed the first ANDA for 80 mg. Newbould added, "Our company is an established leader in pain management and we will voluntarily establish a program to reduce the risk and potential misuse of generic OxyContin."

Commenting on the risk-management program, Jesse Vivian, B.S. Pharm., J.D., professor of pharmacy practice at Wayne State University in Detroit, said that there are currently no industry standards about when risk-management programs are necessary. "It's done on a case-by-case basis, which makes it difficult for the generic industry to navigate."

Whether Endo's voluntary risk-management program will help speed generic OxyContin to market is unclear. What is certain is that the painkiller will be the subject of continued controversy and legal quarrels far into the future.