View attachment 52620 STRATFORD, N.J. — There was a stranger waiting for Sarah Fuller when she visited her doctor to discuss switching medications for her back and neck pain — a saleswoman pitching a prescription version of the potent opioid fentanyl.
The drug, called Subsys, is so powerful, and the risk of addiction and overdose so formidable, that the Food and Drug Administration requires doctors to undergo special training before they are allowed to prescribe it. And it has approved Subsys only for cancer patients who suffer intense flares of pain. Fuller didn’t have cancer. She had been in two car accidents and been diagnosed with painful fibromyalgia. Yet her physician “let the sales rep start talking about helping her with the pain,” David Fuller, who accompanied his daughter to the appointment, told STAT.
Just over a year after that January 2015 office visit, 32-year-old Sarah Fuller was found dead in her bedroom by her fiance. The county medical examiner ruled her death the result of the “adverse effect of drugs.” A toxicology screen revealed a level of fentanyl in her blood that experts consulted by STAT said is lethal. There was also a small amount of the anti-anxiety medication Xanax in her system.
Synthetic forms of fentanyl, most of it illegally shipped from China, have flooded into the US and Canada in the past year, causing hundreds of overdose deaths. But Sarah Fuller’s case shows that the prescription version of the drug can also be dangerous when it’s prescribed “off-label” for conditions it’s not approved for — and that Insys Therapeutics sales reps have encouraged doctors to do just that.
“They killed her,” Sarah’s mother, Deborah Fuller, said of those involved in putting her daughter on a high-dose regimen of fentanyl, which is up to 100 times more potent than morphine. “You took a beautiful girl getting ready for her wedding, something she dreamed of.”
There is no indication her fentanyl use and subsequent death was from anything other than the legal drug she was prescribed for her pain, said Richard Hollawell, a Marlton, N.J., attorney hired by Sarah’s family to investigate her death. He said the family plans legal action against both Insys and Dr. Vivienne Matalon, the Cherry Hill, N.J., physician who prescribed the Subsys.
Telephone messages and emails to Insys’s public relations representative and a company official were not returned. Matalon did not return multiple messages left at her office and home.
While doctors are allowed to prescribe drugs for off-label conditions, drug makers aren’t permitted to promote medications for these purposes. Insys, based in Chandler, Ariz., is under investigation by several state attorneys general and federal prosecutors for the marketing of Subsys, according to disclosures the company has made in public securities filings. On Thursday, federal prosecutors in Connecticut charged a former Insys district sales manager, whose territory included New Jersey, with allegedly paying kickbacks to doctors to get them to prescribe fentanyl.
Insys has already settled one case, in Oregon. The attorney general there alleged Insys was “implicitly misrepresenting to patients that Subsys should be used to treat migraine, neck pain, back pain, and other off-label uses for which Subsys is neither safe nor effective.” Subsys settled the case last year by making a payment of $1.1 million. It did not admit to any improper behavior.
In addition, both an Insys sales rep in Alabama and a nurse in Connecticut have pleaded guilty to federal kickback charges related to off-label Subsys prescribing. Those cases alleged that doctors and a nurse were paid kickbacks by company employees to prescribe the drug. The sales rep in Alabama was paid a base salary of $40,000 but received more than $700,000 in commissions from 2013 to 2015 based on the volume of off-label prescriptions written by doctors she called on, according to court records.
The aggressive and illegal marketing of Subsys comes as the country deals with an epidemic of opioid addiction. It follows other instances of the illegal marketing of opioids that have been blamed for helping to fuel the crisis. In 2007, Purdue Pharma, the maker of the painkiller OxyContin, pleaded guilty to a criminal charge related to its marketing of the drug and paid more than $600 million in fines.
“We have created a system by which [drug] companies go out and break the law, they may or may not get caught, and if they do get caught, they are just going to pay a settlement,” said Eric Campbell, a professor of health policy at Harvard Medical School who also is as an expert witness for the federal government in an ongoing off-label marketing case. “The settlement they pay is going to be less than they make doing these activities. It is just like parking tickets on delivery trucks.”
Sarah Fuller is not the only Subsys patient who is alleged to have died from taking the prescription drug. A case filed in July in Jacksonville, Fla., alleges Carolyn Markland died in 2014, only hours after taking Subsys in her doctor’s office. She was being treated for chronic back pain.
Subsys is the only brand-name drug Insys sells. In 2011, the year before it hit the marketplace, Insys was operating at a loss with no reported revenue. Last year, company revenues were $330 million and it reported a profit of $58.5 million.
The company recently announced that its founder, John Kapoor, would be stepping down as chief executive. According to a March financial filing, Kapoor is the largest shareholder in the company, with a stake valued at just under $600 million based on the most recent closing price of Insys shares.
Sarah first started to heavily use painkillers following an auto accident a decade ago, her family said during an interview inside the modest ranch-style home where Sarah lived just outside Philadelphia.
Her car was broad-sided by another vehicle and she suffered several herniated discs in her back and neck. Just two years earlier, her vehicle had been hit from behind at a stop sign. That accident also left her with spinal pain. It was not long before she was completely dependent on the drugs. She was on so many medications that in 2014, her kidneys failed, according to father, a baker, and her mother, who worked as an office administrator.
Her family said Sarah’s personality and physical condition changed after she became a chronic user of opioids. As a child, she was a standout soccer player. After high school, she worked for several years as an aide at nursing homes. She would frequently pick up extra hours, working back-to-back shifts for additional money. She enjoyed going out with friends.
On the drugs, she was lethargic and unmotivated, her family said. She gained 100 pounds. Walking even as far as the length of the driveway proved difficult. She would spend days in her pajamas and slippers, with the shades drawn.
A printout of her prescriptions from a local Rite Aid pharmacy, beginning in mid-2007 and continuing until her death in March, runs 122 pages. There are 974 individual prescriptions listed, many of them for 30-day supplies and some for longer. The drugs include the painkillers OxyContin and Percocet, antidepressants, and anti-anxiety medications.
Sarah received her first shipment of Subsys on Jan. 9, 2015: a box with a 20-day supply of the 200-microgram dose of the drug, delivered by FedEx. Medicare, which covered Sarah after she was determined to be disabled following a second car accident, paid $5,509 for the prescription, according to a pharmacy billing ledger.
The following month, Sarah’s dosage of Subsys was tripled to 600 micrograms, and the cost to Medicare doubled. In August 2015, Sarah started to receive 30 days of supply instead of 20. Her last delivery was on March 22, 2016, just three days before she died. The box contained 180 doses of Subsys at a cost of $19,657 to Medicare. During the 15 months Sarah was on Subsys, Medicare paid $250,544 for the Subsys she was prescribed, according to a billing ledger prepared by Linden Care, a Woodbury, N.Y., specialty pharmacy.
After starting to take fentanyl, her need for opioids was more intense. Subsys is administered by a spray under the tongue and rapidly enters the bloodstream. It is intended to be taken every four hours. Sarah would set her alarm during the night to make sure she woke up to take a dose on time. If she waited longer than four hours, she would start to shake and become agitated. The drug also intensified feelings of depression, her family said. She would take additional doses at times. Some months, she would run out before her next delivery arrived. To get her through the days she didn’t have Subsys, Sarah would take OxyContin she was also prescribed, her mother said.
Dr. Adriane Fugh-Berman, a physician and Georgetown University professor who helped the District of Columbia develop training programs for opioid prescribers, said the high doses of fentanyl prescribed to Fuller were likely inappropriate.
“They don’t work well for chronic pain,” she said of drugs like Subsys. Over the long-term, daily use of high doses of fentanyl can reduce oxygen levels in the blood. The respiratory system is depressed, and Fugh-Berman said it is not uncommon for some people on heavy doses of opioids to die in their sleep.
Asked about the presence of the Insys drug rep in the doctor’s meeting with Fuller, Fugh-Berman called it a “new level of outrageous behavior and inappropriateness.” Hollawell, the lawyer representing the Fuller family, said he confirmed the sales rep was at the meeting from notes kept in Sarah’s medical file at her doctor’s office. The amount of fentanyl found in Sarah’s blood after she died was 15 to 20 times the therapeutic level and well above rates considered lethal, said Dr. Lewis Nelson, the chair of emergency medicine at Rutgers New Jersey Medical School. “This is clearly a fentanyl death,” he said.
“It’s very possible she was just on this drug chronically and overdosed a little bit,” Nelson said. “She either took too much by accident or by purpose.”
Subsys, Nelson added, is being “marketed well beyond its indicated use.”
By David Armstrong - STAT/Sept. 30, 2016
Photos: 1-Matthew Orr; 2-Dominic Reuter; inset- Richard Hallowell