Wyeth Pharmaceuticals: A Kidney Drug With an All-Transplant Sales Target

In the Wyeth Rapamune settlement, drug maker Wyeth Pharmaceuticals agreed to pay $257.4 million to settle civil allegations over off-label promotion of its transplant drug. That civil settlement was part of a $490.9 million overall resolution. The government described a national sales campaign that trained and rewarded representatives for reaching beyond kidney transplant patients. Its civil allegation followed the prescriptions to the bill: some promoted uses lacked coverage, yet government health programs paid.

The Department of Justice announced the resolution on July 30, 2013. The civil allegations in this pharmaceutical fraud case covered promotion from 1998 through 2009.

What Rapamune Was Approved For

Rapamune, also known as sirolimus, is an immunosuppressant that prevents the body’s immune system from rejecting a transplanted organ. The Food and Drug Administration approved it for kidney transplant patients in 1999. According to the whistleblower’s complaint, that approval covered de novo use, immediately after transplantation, in combination with cyclosporine and corticosteroids.

In the pharmaceutical business, a product’s label describes a particular use and treatment setting. For Rapamune, changing the transplanted organ, switching a patient from another immunosuppressant or changing the accompanying drugs could move the treatment beyond the approved use. Those were the categories the government identified in the civil settlement. A sales plan built around all transplant patients therefore reached a different market from the one described by the kidney-transplant approval.

What Is Considered Off-Label Promotion?

Off-label promotion is marketing a drug for uses its approval does not cover. In the Rapamune case, the government alleged promotion for non-renal transplants, conversion from another immunosuppressant to Rapamune, and combinations with other immunosuppressants not listed on the label. The whistleblower’s complaint identified liver, heart, pancreas, islet and lung transplant patients among the populations Wyeth allegedly targeted.

The Justice Department described national sales-force training, materials on non-renal transplant use and instruction on presenting those materials to transplant physicians. Financial incentives encouraged representatives to target all transplant populations. Bonuses made the wider market part of the sales job.

That sequence matters to an insider. Training materials show what representatives were equipped to say. The target population shows where management wanted the message delivered. Incentive compensation shows which sales the company rewarded. Together, those records can explain how a promotional strategy reached the field.

Liver-Transplant Training After the Warning

The whistleblower’s complaint alleged that Wyeth marketed Rapamune to liver transplant patients from 2003 through approximately 2006 despite a May 2002 boxed warning about graft loss and death. It then identified the training materials that allegedly carried the campaign forward.

According to the complaint, a March 2003 sales-training binder included a lesson on diseases leading to liver transplantation and a chapter devoted to liver transplantation. The materials allegedly linked that teaching to Rapamune treatment and told representatives that Rapamune could avoid kidney toxicity associated with other immunosuppressants in liver transplant patients.

The dates give the allegation its force. The warning had arrived before the training binder. The complaint describes a company continuing to prepare its sales force for the very patient population the warning addressed. For a transplant patient, the concern was loss of the transplanted organ or life itself. For the sales force, that population remained part of the alleged opportunity.

Paid Presentations and a Different Audience at Conventions

The complaint also alleged that the promotional message traveled through physicians paid by Wyeth. In its account of a company-sponsored continuing medical education program, the whistleblower alleged that consultant payments bought false off-label presentations to other doctors. Through these paid physician presentations, the company’s pitch allegedly reached prescribers in a fellow doctor’s voice.

The same complaint alleged a striking limit on who should hear from the sales force at national conventions:

The alleged instruction was specific enough to include the geography on a visitor’s name tag. A company preparing representatives to discuss the drug with transplant physicians was allegedly also preparing them to avoid discussing it with its regulator.

Business Plans Kept Off the Computer

In the complaint’s account, representatives promised not to push conversions, then won management praise for securing them. Beginning in 2007, Wyeth allegedly required representatives to certify that they would not promote unapproved uses, including conversion protocols. Yet the whistleblower alleged that a senior transplant-sales executive praised representatives in March 2008 for securing a hospital protocol change calling for conversion to Rapamune.

That same month, a sales director allegedly encouraged a representative to keep business plans handwritten instead of entering them in the company’s computer system. The complaint put the formal restriction, the management praise and the instruction about business plans side by side. An insider who heard those messages could explain the distance between the written rule and the sales direction.

How Promotion Reached Government Claims

The government alleged that some of the promoted Rapamune uses were not medically accepted indications and therefore lacked coverage under Medicare, Medicaid and other federal health care programs. Wyeth’s promotion allegedly caused false claims for those uses. That payment connection made the sales campaign a False Claims Act case.

The complaint described the handoff: Wyeth’s marketing influenced physicians’ prescriptions, and pharmacies or other providers submitted the resulting bills. The manufacturer controlled the promotion while another business could send the claim to the government. The complaint alleged that taxpayers paid at the end of that chain.

The company’s own sales intelligence allegedly helped connect those decisions. The complaint said Wyeth tracked whether Rapamune prescriptions involved kidney or other organ transplants, whether patients switched from another drug, and which immunosuppressants accompanied Rapamune. Field activity reports and marketing records allegedly captured the same distinctions that mattered to the payment allegations.

That is why the prescribing detail matters as much as the pitch. A presentation describes the use a company promotes. A report identifying transplant type or a drug combination can connect that message to what physicians actually prescribed. We examine that connection with the insider, alongside the claims and the coverage at issue.

The importance of medically accepted indications also appeared in Amgen’s promotion case. In its civil allegations announced in December 2012, the government contended that Amgen improperly obtained listings in medical reference works to make off-label uses eligible for government coverage, using journal articles insufficient to support their safety and effectiveness. Rapamune’s civil allegations likewise depended on the connection between the promoted use and the public program’s payment.

The Insiders Behind the Civil Cases

Two former Rapamune sales representatives and a pharmacist brought the two qui tam cases resolved by the civil settlement. One case came from a former representative and the pharmacist together. Another former representative brought the other.

Those roles place pharmaceutical whistleblowers at different points in the healthcare business. A sales representative can explain the training, instructions and incentives behind a prescribing campaign. Pharmacy knowledge can help connect a prescription to the dispensing and billing that follow. The Rapamune complaint’s attention to field reports shows why an insider’s understanding of ordinary business records can matter as much as an explicit instruction to promote a particular use.

A 2018 Public Citizen study of pharmaceutical industry settlements found that whistleblower revelations were responsible, at least in part, for 92 of the 170 federal settlements it identified from 1991 through 2017. People who understood the business helped bring the payment problem into view.

What the Civil Settlement Required

Wyeth agreed to pay $230,112,596 to the federal government and $27,287,404 to the states.

A whistleblower case under the False Claims Act can pay 15% to 30% of what the government recovers.

Pfizer’s Acquisition and the Sales Force It Inherited

Pfizer acquired Wyeth in 2009. The government attributed the Rapamune promotion to Wyeth, while the later compliance obligations reached former Wyeth employees working in Pfizer’s sales and marketing functions.

The Justice Department said Pfizer’s existing Corporate Integrity Agreement with the Department of Health and Human Services’ Office of Inspector General covered those employees. Pfizer had entered that agreement in another matter shortly before the acquisition. It required risk assessments, a confidential disclosure program, auditing and monitoring to identify improper marketing.

You Know How the Campaign Reached the Field

If you know the transplant-center pitch, the sales incentives or the prescribing reports behind a drug campaign, talk to our whistleblower experts about what you saw. We work with you to build your strongest pharmaceutical whistleblower case and bring in pharmaceutical whistleblower lawyers who understand off-label promotion. We stay with you as partners throughout the case.