Amy Ritter was Scientific Editor, BioPharm International.

Amy Ritter, PhD

Amgen has pleaded guilty to a single misdemeanor count for illegally introducing a misbranded drug into interstate commerce and has agreed to pay $762 million to resolve criminal and civil liability arising from its sale and promotion of certain drugs. 

, the government alleged that Amgen promoted their erythropoiesis-stimulating drug, Aranasep, for off-label use. Aranasep was approved by FDA at calibrated doses for particular patient populations suffering from anemia. In order to increase sales of Aranesp, the government said that Amgen illegally sold the drug with the intention that it be used at off-label doses that FDA had specifically considered and rejected, and for an off-label treatment that FDA had never approved. 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 to resolve allegations 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, Enbrel and Neulasta, for off-label uses and doses that were not approved by FDA and not properly reimbursable by federal insurance programs 

Offered illegal kickbacks to a wide range of entities in an effort to influence health care providers to select its products for use 

Engaged in false price reporting practices involving several of its drugs.

As part of the global settlement, Amgen has also agreed to enter into a corporate integrity agreement with the Department of Health and Human Services that will govern its conduct, and ensure careful oversight of its branding and marketing practices.

"The government raised important concerns in the criminal prosecution. Amgen acknowledges that mistakes were made, and we did not live up to our standards," said Cynthia M. Patton, senior vice president and chief compliance officer at Amgen in a company 

. "This Corporate Integrity Agreement is aligned with the significant changes and enhancements we have made to our compliance program and demonstrates our commitment to fostering a culture of compliance at Amgen."

Articles

Amgen has agreed to pay $762 million to resolve criminal liability and false claims act allegations.

Amgen Settles False Claims Act Allegations

 raxibacumab injection to treat inhalational anthrax, a form of the infectious disease caused by breathing in the spores of the bacterium 

. Raxibacumab is also approved to prevent inhalational anthrax when alternative therapies are not available or not appropriate. Raxibacumab is a monoclonal antibody that neutralizes toxins produced by 

Raxibacumab was developed by Human Genome Sciences (HGS) in conjunction with the Biomedical Advanced Research and Development Authority (BARDA) of the Office of the Assistant Secretary for Preparedness and Response (ASPR), US Department of Health and Human Services (HHS). HGS was acquired by GlaxoSmithKline in July, 2012, making raxibacumab part of GSK’s portfolio.

Raxibacumab is the first monoclonal antibody approved under FDA’s Animal Efficacy Rule, which allows efficacy findings from adequate and well-controlled animal studies to support FDA approval when it is not feasible or ethical to conduct trials in humans. In this case, because inhalational anthrax is a rare and lethal disease, it is not possible to conduct adequate efficacy trials in humans. 

In addition, the drug is the first to be developed under Project Bioshield to receive FDA approval, according to a 

 from HHS.  The Project Bioshield Act was signed in 2004 and provides funding to support and expedite the development and procurement of medical countermeasures against chemical, biological, radiological, and nuclear threats. According to GSK’s 

, the US Government is currently the sole recipient of raxibacumab supplies. 

Anthrax antitoxin is the first monoclonal antibody approved under FDA's Animal Efficacy Rule, and the first product from BARDA's Project Bioshield to receive FDA approval.

FDA Approves First Anthrax Antitoxin

Pfizer has agreed to pay $55 million plus interest to settle charges that Wyeth (acquired by Pfizer in October 2009) improperly promoted the drug Protonix (pantoprazole). Protonix is a proton pump inhibitor used to treat forms of gastro-esophageal reflux disease (GERD). It was approved for short-term treatment of erosive esophagitis, a condition that could only be diagnosed using endoscopy. The US Department of Justice, however contends that Wyeth promoted Protonix for treatment of all forms of GERD, including more common forms that could be diagnosed without endoscopy.

, the government alleges that Wyeth trained its sales force to promote Protonix for all forms of GERD, beyond its limited erosive esophagitis indication, and that Wyeth sales representatives frequently promoted Protonix to physicians for unapproved uses, such as symptomatic GERD. In addition, Wyeth allegedly promoted Protonix as the “best PPI for nighttime heartburn” even though there was never any clinical evidence that Protonix was more effective than any other PPI for nighttime heartburn. Finally, the government claims that Wyeth used continuing medical education programs as promotional vehicles for off-label use.

The claims settled by this agreement are allegations only. Pfizer denies these allegations, and there has been no determination of liability. Since August 2009, Pfizer has been under a Corporate Integrity Agreement with the Department of Health and Human Services, which agreement remains in effect.

Pfizer has agreed to pay USD 55 million plus interest to settle charges that Wyeth (acquired by Pfizer in October 2009) improperly promoted the drug Protonix (pantoprazole).

Pfizer Settles Off-Label Promotion Charges

 that they have entered into a global collaboration agreement to discover and develop antisense drugs against three undisclosed targets to treat neurological or neuromuscular disorders. Isis will be responsible for development of the drugs through the completion of the initial Phase 2 clinical trial, with Biogen Idec providing advice and assistance on research, clinical trial design and conduct, and regulatory strategy for each program. Biogen Idec has the option to license a drug from each of the three programs through the completion of Phase 2 trials, and if it exercises its option, Biogen Idec will be responsible for global development, regulatory, and commercialization.

In the accompanying press release, Richard Brudnick, vice-president and co-head of business development at Biogen Idec said, "This will be our third collaboration with Isis, which is reflective of our respect for them as a partner and as a leader in antisense technology. By combining Isis' knowledge with Biogen Idec's expertise as a leader in neurology, we believe this latest discovery collaboration holds great potential for finding novel approaches to treating neurologic diseases."

Biogen Idec and Isis Pharmaceuticals announced that they have entered into a global collaboration agreement to discover and develop antisense drugs against three undisclosed targets to treat neurological or neuromuscular disorders.

Biogen Idec and Isis Pharmaceuticals to Collaborate on Antisense Programs

Endo Pharmaceuticals, maker of the opioid medication Opana ER (oxymorphone HCl), is suing FDA to prevent generic manufacturers from entering the market with formulations of oxymorphone that are not abuse-resistant. Endo voluntarily withdrew its older formulation of Opana ER in March, 2012, and launched a crush-resistant version to replace it. According to Endo’s Nov. 30, 2012 

 , the lawsuit, filed in the US District Court for the District of Columbia, is based on the failure of the FDA to meet its legal obligation to determine in a timely manner whether the old formulation of Opana ER was withdrawn from the market for reasons of safety. If, as Endo claims, the reformulation was done for reasons of safety, then generic manufacturers will have to introduce products that reproduce the new formulation. Critics point out, however, that the reformulation was conveniently timed to coincide with Opana’s patent expiry, and might easily be construed as a tactic to delay entry of generic competition.

		Health Canada recently approved generic opioids containing the old formulations, a move that was not well received by those concerned that the availability of low-cost generics would exacerbate the problem of prescription opioid abuse. However, according to a Nov. 19, 2012 

 from Health Canada, there is no basis in Canada’s Food and Drugs Act to withhold approval of a drug where the drug is otherwise considered safe and effective for its recommended use. The law does not permit approval to be withheld on the basis of misuse. Canada’s approval of those products has sparked concern that they may find their way over the border and into the US as street drugs, according to a 

		US regulators are operating under similar constraints as Canadian regulators, which makes for difficult policy. FDA recognizes that prescription opioid abuse is a serious public health problem, which the Agency has attempted to counter with a 

 introduced in July 2012. On the other hand, inexpensive generics are beneficial to payers and to patients legitimately in need of pain medication. It’s hard to see which way FDA will go. Deterring prescription drug abuse is good public policy, but it may not be within FDA’s mandate to make that policy decision.

Endo Pharmaceuticals, maker of the opioid medication Opana ER (oxymorphone HCl), is suing FDA to prevent generic manufacturers from entering the market with formulations of oxymorphone that are not abuse-resistant.

Opioid Formulation: Out with the Old

Eli Lilly released its annual report containing updates on progress and new initiatives in corporate responsibility. The 

 contains updates on longstanding programs, as well as data for 2011. The report also serves as the company's annual Communication on Progress to the United Nations Global Compact (UNGC). As a signatory of the UNGC, Lilly shares its progress annually on 10 principles related to human rights, labor, the environment, and anticorruption.

Included in the report are highlights indicating that Lilly:

Gave more than $590 million in charitable contributions in 2011, including cash, products, and other in-kind donations, and also including contributions made through the company's patient assistance programs

Introduced The Lilly Global Health Innovation Campaign. The campaign encompassses two corporate responsibility programs, the Lilly NCD Partnership and the Lilly MDR-TB Partnership, aimed at improving health for people in need in developing countries

Received a perfect score of 100 on the Human Rights Campaign's "Best Places to Work: Corporate Equality Index" in 2011

Selected 200 employees to volunteer two weeks each, on company time, in countries where people lack resources or access to quality healthcare

Reduced serious injury and lost-time injury rates each by 50% since 2007

Decreased water intake by more than 25% and waste to landfill by 40% compared with 2007

Improved energy efficiency by more than 15% compared with 2007, and reduced corresponding greenhouse gas emissions by more than 15%.

"Increasingly, we are integrating the concept of 'shared value' into the way we operate," said John C. Lechleiter, PhD, Lilly chairman, president and chief executive officer in a company 

. "Using our business expertise to help address pressing social needs opens up new opportunities for us to provide solutions to health challenges the world over. We believe this approach will help to create enduring value for society and for Lilly."

Eli Lilly released its annual report containing updates on progress and new initiatives in corporate responsibility.