U.S. District Judge Sterling Johnson, Jr., accepted a guilty plea by biotechnology giant Amgen for illegally introducing a misbranded drug into interstate commerce Dec. 19 in Brooklyn, N.Y. The plea is part of a settlement with the U.S., in which Amgen agreed to pay $762 million to resolve criminal and civil liability arising from its sale and promotion of certain drugs, according to the Department of Justice (DOJ).
The settlement represents the single largest criminal and civil False Claims Act settlement involving a biotechnology company in U.S. history.
As part of the plea agreement and criminal settlement, Thousand Oaks, Calif.-based Amgen entered a guilty plea Dec. 18 before Johnson of the Eastern District of New York to criminal information charging the firm with illegally introducing a misbranded drug, Aranesp, into interstate commerce.
Under the Food, Drug and Cosmetic Act, it is illegal for drug companies to introduce into the marketplace drugs that the company intends will be used “off-label,” i.e., for uses or at doses not approved by the FDA, according to the DOJ. Aranesp is an erythropoiesis-stimulating agent (ESA), which is approved by the FDA at calibrated doses for particular patient populations suffering from anemia. “[T]o increase sales of Aranesp and reap the resulting profits, Amgen illegally sold the drug with the intention that it be used at off-label doses that the FDA had specifically considered and rejected, and for an off-label treatment that the FDA had never approved,” the DOJ stated.
Under the terms of the criminal plea agreement, Amgen will pay a criminal fine of $136 million and criminal forfeiture in the amount of $14 million.
As part of the civil settlement, Amgen has agreed to pay $612 million ($587.2 million to the U.S. and $24.8 million to the states) to resolve claims that it caused false claims to be submitted to Medicare, Medicaid and other government insurance programs. The federal civil settlement agreement encompasses allegations that Amgen:
- Promoted Aranesp and two other drugs that it manufactured, Enbrel and Neulasta, for off-label uses and doses that were not approved by the FDA and not properly reimbursable by federal insurance programs;
- Offered illegal kickbacks to a wide range of entities in an effort to influence healthcare providers to select its products for use, regardless of whether they were reimbursable by federal healthcare programs or were medically necessary; and
- Engaged in false price reporting practices involving several of its drugs.
As part of the settlement, Amgen has also agreed to enter into a corporate integrity agreement with the U.S. Department of Health and Human Services and the Office of the Inspector General that will govern its conduct and oversee its branding and marketing practices.
“Instead of working to extend and enhance human lives, Amgen illegally pursued corporate profits while jeopardizing the safety of vulnerable consumers suffering from disease,” said Acting U.S. Attorney of the Eastern District of New York Marshall L. Miller, JD, in a release. “To all who might consider introducing misbranded drugs into the marketplace, you are on notice: we remain steadfastly committed to prosecuting such violations of law.”
Beginning at the launch of Aranesp in 2002 and extending until 2007, the DOJ reported that Amgen illegally introduced Aranesp for uses and at dosage levels that the FDA had specifically declined to approve due to insufficient clinical evidence to establish their safety and efficacy. In particular, Amgen illegally introduced Aranesp into the oncology and nephrology ESA markets, intending that it be used for patients suffering from anemia due to chronic kidney disease or chemotherapy at off-label, unapproved doses that were larger and less frequently administered than those approved by the FDA for these patient populations. Amgen also illegally introduced Aranesp into the oncology ESA market intending that it be used to treat anemia caused by cancer, irrespective of whether the patient had been prescribed chemotherapy—a use which the FDA had never approved and which the agency subsequently determined caused an increased risk of death.
In 2007, the FDA issued a black-box label for Aranesp’s label, warning that the drug “increased the risk of death . . . in patients with active malignant disease [cancer] receiving neither chemotherapy nor radiation.” At approximately the time that the FDA issued the black-box warning, the DOJ said that Amgen ceased its promotion of Aranesp for the treatment of anemia caused by cancer rather than the cancer’s treatment.
Amgen’s misbranding of Aranesp was the company’s core business strategy to gain market share from its only ESA competitor, Procrit, sold by Johnson & Johnson. To compete with Procrit, Amgen built the Aranesp commercial strategy around the unapproved, off-label approach of a less frequent dosing schedule, which Amgen sales representatives argued was more convenient for patients and more profitable for doctors, according to the Justice Department.
Aware that its misbranding of Aranesp was illegal, Amgen instructed its sales representatives to promote off-label uses through the guise of “reactive marketing,” the DOJ reported. Amgen thus trained its sales representatives to intentionally elicit questions from doctors about off-label uses as legal cover to then provide the doctors with studies supporting the off-label use, thereby promoting the drug for that unapproved use. The studies that Amgen provided to doctors to support off-label uses were often the very same studies that the FDA had rejected as insufficient to support the safety and efficacy of those off-label uses, when Amgen had applied to expand Aranesp’s label to encompass them.
The $612 million civil settlement encompasses broader allegations by the U.S. against Amgen than those contained in the Information. The civil settlement agreement resolves claims contained in 10 lawsuits against Amgen that were brought under the qui tam, or whistle-blower, provisions of the False Claims Act, which allow private citizens to bring civil actions on behalf of the U.S. and share in any recovery. Seven of these cases currently are pending in the Eastern District of New York; two are pending in the District of Massachusetts and one in the Western District of Washington.
In the civil settlement, the U.S. contended that between September 2001 and September 2011, Amgen “knowingly promoted” the sale and use of Aranesp for dosing regiments and indications which were not approved by the FDA, and not medically accepted indications, including anemia caused by cancer, anemia caused by chronic disease, chronic anemia and anemia caused by myelodysplastic syndrome. The U.S. further contended that Amgen used journal articles that were insufficient to support the safety and efficacy of the off-label uses at issue, and improperly obtained listings in medical compendia in an effort to establish that the off-label uses were medically accepted, and thereby eligible for coverage by federal healthcare programs. The U.S. also contended that Amgen similarly promoted its drugs Enbrel and Neulasta for off-label indications that were not eligible for coverage by federal healthcare programs. The civil settlement agreement also covered claims that Amgen knowingly reported inaccurate pricing information.
In a separate civil settlement, International Nephrology Network (INN), renamed Integrated Nephrology Network, a subsidiary of AmerisourceBergen, also has agreed to pay $15 million to resolve civil liability arising from its role in the marketing of Aranesp. The agreement encompasses claims that INN offered illegal kickbacks to influence healthcare providers’ selection of Aranesp for treatment of kidney disease and in so doing also caused false price reporting for Aranesp. This agreement resolves a single qui tam action.