Unredacted complaint reveals fentanyl manufacture Teva/Cephalon’s illegal marketing strategies

~ Newly unsealed information shows for the first time the extent to which Teva/Cephalon lied about the uses and risks of their fentanyl drugs to boost sales ~

RICHMOND (February 10, 2020) – Newly unsealed information shows for the first time the extent to which Teva Pharmaceuticals, USA, Inc. and its predecessor Cephalon Inc. lied about the uses and risks of their fentanyl drugs to boost sales. The scale of Teva and Cephalon’s lies and deception was revealed in a newly unredacted Complaint in Attorney General Mark Herring’s lawsuit against the companies for their role in creating and perpetuating the opioid crisis through their unlawful, decades-long campaign to boost sales and deceive the public about these drugs. The unredacted Complaint shows how the companies took opioids the FDA had only approved for treating cancer patients’ pain and aggressively marketed them for a wide variety of prohibited off-label uses and encouraged non-cancer treating doctors, a third of whom were primary care physicians, to misprescribe these powerful drugs; discloses the FDA’s previously unknown stern warnings about the drugs, which the companies subsequently ignored; and shows how the companies manipulated clinical trial data to hide what they knew about their drugs’ addiction and overdose risks and how they exaggerated the drugs’ overall efficacy and benefits.

“Teva and Cephalon blatantly lied about the usage, the efficacy, and the risks of their extremely dangerous and addictive drugs in order to make billions of dollars in profit,” said Attorney General Herring. “Families in Virginia and around the country have been devastated by the ongoing opioid epidemic, which has its roots in the boardrooms and marketing departments of companies like Teva and Cephalon. This unredacted Complaint reveals how these opioid manufacturers had absolutely no problem with putting human lives at risk in order to make as much money as they could. I will not stop until pharmaceutical companies are held accountable and shoulder the financial burden for their role in creating and prolonging the opioid crisis.”

Since 2007, fatal fentanyl overdoses in Virginia have risen by nearly 1,600%, from just 48 in 2007 to more than 800 in 2018. In the same period, nearly 10,000 Virginians have died of a heroin or opioid overdose, including 5,700 from a prescription overdose, and nearly 3,500 from a fentanyl overdose, all while Teva/Cephalon made huge sums of money from its fentanyl drugs.

In October 2019, Attorney General Herring filed suit against opioid manufacturer Teva/Cephalon for engaging in what he alleges was an unlawful, complex, decades-long campaign to boost sales of fentanyl – the most potent narcotic currently approved for human use – by marketing its rapid acting fentanyl drugs for unapproved and unsafe uses, and by knowingly and intentionally downplaying the risks of its drugs while overselling the benefits.

Unlawfully Marketing and Promoting Cancer Pain Drugs for Non-Cancer Related Conditions
In 2008, Cephalon settled federal criminal charges and state civil charges for illegally marketing Actiq, a potent rapid-release form of fentanyl, which was administered via a raspberry-flavored fentanyl lollipop. Attorney General Herring’s unredacted Complaint reveals the involvement of Cephalon’s top managers in targeting and encouraging doctors to prescribe Actiq for a wide range of unapproved symptoms and issues, including “acute pain, premedication for procedures, post-surgical pain, kidney stones, tooth extractions, migraine pain, back pain, neuropathic pain, headache pain, arthritis, or fibromyalgia.”

The unredacted Complaint shows how these managers participated in conferences at high-end resorts, where they ostensibly “educated” high prescribers of other opioids about the benefits of Actiq for uses forbidden by the FDA using “educational” materials that they never submitted to the FDA. The unredacted Complaint shows how the conferences persuaded providers to go back to their home states, including Virginia, and use Actiq for unsafe and unapproved uses, all while Cephalon was telling the FDA it was discouraging the uses.

One email from a Cephalon agent to Andy Pyfer, Cephalon’s brand manager for Actiq, captures the company’s sales goals efforts at the time, summarizing a well-attended conference at a five-star San Diego resort by saying: “It was a great meeting. I think we definitely sold some Actiq.”

The unredacted Complaint also reveals for the first time the scope of Cephalon’s illegal sales practices at this time. It shows Cephalon aggressively targeted non-cancer prescribers and doctors with sales and promotional visits, including doctors specializing in “primary care, family medicine, physical medicine, and neurology,” even though the drugs were only FDA approved to treat cancer patients. Below is a breakdown of Cephalon’s sales calls in the first seven months of 2004:

The unredacted Complaint also reveals Cephalon’s “ride ‘em up ride ‘em down policy,” which encouraged salespeople to repeatedly target high prescribers up until the point authorities stepped in and stopped the prescriber. As the Complaint explains: “as a high-performing Florida salesperson put it about a high prescribing doctor…‘i[f] I knew that this physician was in town practicing medicine, I would’ve been in there three times a week pushing him to write more Actiq’”. Cephalon even “affirmatively told salespeople not to report or flag doctors who salespeople knew were prescribing Fentora off-label for the wrong conditions”.

Cephalon Ignored FDA Warnings
The unredacted Complaint reveals a previously unknown series of meetings between the FDA and Cephalon in 2004, in which top FDA officials warned Cephalon that the use of Actiq by non-cancer patients was “staggering…the Agency is very concerned that the situation that occurred with Oxycontin may happen again.” The FDA told Cephalon its sales practices were creating a “significant public health” problem, by providing non-cancer patients with a product so powerful it put them at risk of an immediate overdose.

The unredacted Complaint also reveals that Cephalon did not substantially change its practices with the introduction of Actiq’s successor Fentora, in 2006, a rapid-release fentanyl tablet. The company kept targeting providers who were prescribing Fentora for back pain, and other non-cancer conditions, and it kept turning a blind eye to the resulting problems.

Below is an egregious example of a company-approved response to a Q&A produced for their salespeople:

Knowingly Downplaying Risks of Abuse and Overdose While Overselling Benefits and Efficacy
The unredacted Complaint discloses clinical trial data showing that Cephalon and then Teva, which acquired Cephalon in 2011, knew Actiq and Fentora were widely abused and misused by clinical trial patients and knew the drugs were showing potentially alarming diminution in pain relief the longer the patients used them.

The unredacted Complaint reveals that data from clinical trials of Fentora showed that the drug “increased the risk of addiction while bringing fleeting and diminishing relief” and that “patients taking Actiq or Fentora for months or longer exposed themselves to extremely high risks and diminishing pain relief.” According to the unredacted Complaint, in one 18 month clinical trial patients had a:
• 31% increase in pain episodes per day, from 3.5 to 4.6 episodes/day;
• Took 26% more Fentora tablets per day, from 3.5 to 4.4 tablets/day; and
• Had a 42% increase in their average daily Fentora dosage, from 2,162 mcg/day to 3,088 mcg/day.

The companies ghostwrote publications in prominent academic journals, like Cancer, that deliberately misled prescribers and patients about these potential declines in the opioids’ pain relieving properties over time. As the unredacted Complaint notes of the Cancer publication about a long-term study of Fentora use by cancer patients, “the actual study data…suggested the opposite of what Cephalon claimed: that the patients who were in study for 12 months or more actually experienced a decline in analgesic efficacy, suggesting an increase in incremental tolerance to Fentora because they were taking more and more doses per day of Fentora and other opioids.” The unredacted Complaint shows that Teva made efficacy claims a “key pillar” of its marketing campaigns for Fentora from 2008 to the present, all while relying on misleading data.

Additionally, the companies were well aware of, but largely did not disclose, alarming clinical trial data about misuse, abuse, and addiction involving Fentora. The unredacted Complaint details how clinical trial patients in long-term cancer and non-cancer trials, none of whom had a history of substance abuse, started exhibiting alarming drug seeking behaviors, what the companies called “aberrant drug related behavior.”

For example, in one non-cancer long-term clinical trial there were frequent incidents of abuse and misuse:
• 11 patients overdosed;
• One patient’s husband overdosed;
• 35 patients reported their Fentora stolen;
• Dozens of patients dropped out of the trial without accounting for the 100-plus Fentora tablets they had been given; and
• Five study centers reported Fentora stolen from supposedly secured lockers.

The company claimed in limited disclosures to regulators like the FDA and its European Union counterpart, that the rates of aberrant drug related behavior in study patients were around 17%. Both the FDA and the EU thought this was alarming, and Cephalon’s internal discussions showed that medical staff believed this 17% rate could rise to “more than 41%” if patients took Fentora and other opioids for a year or more.

The unredacted Complaint also alleges that in marketing materials and publications disseminated to healthcare providers, academics, and the public, Teva and Cephalon knowingly omitted this data, failing to list these serious cases of misuse and abuse in its tables of adverse events, all while claiming its products were “generally safe” and “well tolerated.”

Attorney General Herring’s Work to Address the Opioid Crisis
As part of his ongoing efforts to hold pharmaceutical companies accountable for their role in creating and prolonging the opioid crisis, Attorney General Herring has also filed suit against Purdue Pharma and members of the Sackler Family, the owners of Purdue, alleging decades of illegal conduct designed to enrich the company and family by selling the most opioids possible. In his suit against the Sackler family, filed in September 2019, Attorney General Herring also alleges that the family fraudulently extracted billions of dollars from the company in an effort to put the money beyond the reach of investigators and those suing the company.

Attorney General Herring also continues to participate in a bipartisan, multistate effort to investigate and hold opioid manufacturers and distributors accountable for their roles in the opioid crisis.

The heroin and prescription opioid epidemic has been a top priority for Attorney General Herring. He and his team continue to attack the problem with a multifaceted approach that includes enforcement, education, prevention, and legislation to encourage reporting of overdoses in progress, expand the availability of naloxone, and expand access to the Prescription Monitoring Program. He has supported federal efforts to improve the availability of treatment and recovery resources and made prescription drug disposal kits available across the Commonwealth.

Download the unredacted complaint here.