Death by Fentanyl

The Lucrative Lifesaver

Politicians like Hillary and Obama are promoting a wonder drug to save opiate addicts from deadly overdoses. Its rising cost is enriching some of the same prescription drugmakers who produce the addictive opiates in the first place.

By Connie Fossi
Additional reporting by Cristina Costantini and Adam Weinstein

Heroin and fentanyl almost killed 27-year-old David Harak multiple times since he first started using as a teenager — “probably six times,” he said.

Fentanyl, a high-octane painkiller first prescribed to terminal cancer patients in the 1970s, hit the street big time in the ’90s as a heroin additive. But the potent drug — 100 times more powerful than morphine, and about 50 times stronger than heroin itself — soon became popular as a fix in its own right for users like Harak, so much so that illicit drugmakers now produce their own fentanyl recipes for street distribution. It’s so strong that overdosing on recreational fentanyl is not a matter of if, but when, experts say.

“Heroin addicts run into the fire,” Harak said. “You know somebody overdosed from it. It must be good. You're gonna do exactly what they did. It's just the name of the addiction.”

But each time he overdosed, Harak — who now attends a packed addiction recovery center in Boston — was rescued from death by another miracle of modern medicine: naloxone, a powerful so-called reversal drug, exploding in demand and cost, and produced by some of the same pharmaceutical companies that produce the prescription opioid painkillers that got many addicts hooked in the first place.

An investigation by Fusion found at least three major manufacturers of lifesaving naloxone also produce some of the most potent, addictive pain medications at the heart of America’s narcotics crisis. And a Fusion survey of 12 first-responder agencies across the country found that the naloxone provided to them by drug manufacturers has more than doubled in price since 2010.

That irony is not lost on Harak, who likens the drugmakers to “the house in Las Vegas”: The companies always win. “Do you want to get better? Pay us. Do you want to get worse? Pay us.”

‘Benefit patient care and build shareholder value’

Also known by the brand name Narcan, naloxone has been in use to treat opioid overdoses since the 1970s — not just for heroin, but for legal prescription pain meds like morphine, codeine, oxycodone, fentanyl, and Vicodin. But prescription painkiller overdoses have more than tripled since 2001, now killing more Americans than any other drugs, and as the country grapples with a new fatal opioid epidemic, naloxone has become a powerful political panacea for governors, attorneys general, cops, and even presidential candidates.

Narcan briefly got center-stage treatment during the Democratic presidential debate on Jan. 17, where the three candidates were vying for votes in early-primary states like New Hampshire, ground zero for the new national addiction crisis. “Everywhere I go to campaign, I’m meeting families who are affected by the drug problem that mostly is opioids and heroin now,” former Secretary of State Hillary Clinton told the audience. To solve the epidemic, she said, “Police officers must be equipped with the antidote to a heroin overdose or an opioid overdose, known as Narcan. They should be able to administer it. So should firefighters and others.”

The White House, too, is supporting naloxone: In his proposed 2016 budget, President Obama expanded on a 2011 “prescription drug abuse prevention plan,” pledging tens of millions in new state grants to fight opioid overdose-related deaths, including $12 million to buy naloxone and train emergency responders on how to use it.

That higher profile also translates to increased demand, which has led to price spikes in the last two years. It’s also led to greater interest from pharmaceutical companies and their shareholders, who are bringing more naloxone products to market, much the same way some developed dangerous addictive pain drugs like oxycodone and fentanyl.

For example, Insys Therapeutics, a prescription drugmaker that derived nearly all of its rapidly-growing revenue in recent years from fentanyl, is under investigation by multiple state and federal agencies, and has been scrutinized by media organizations large and small, for allegedly enticing doctors to widely prescribe the lethal narcotic for minor maladies such as back pain. (For the latest on the controversy over Insys, watch Fusion’s hourlong investigative documentary, Death By Fentanyl.) Last fall, as the investigations mounted and Insys’ stock price fell, the company made a much-anticipated announcement: It had been fast-tracked by the Food and Drug Administration to develop its own overdose-combating naloxone spray. The news “will allow us to advance our program to address a significant unmet medical need in the market,” Insys’ then-CEO, Michael Babich, said, adding that his company’s naloxone product would “benefit patient care and build shareholder value.”

In the month following the announcement, Insys’s flagging stock climbed up 24 percent. Reached by phone and email, Insys representatives did not comment on Fusion’s questions about the company’s upcoming Naloxone product by publication time.

Eric Pahon, a spokesman for the Food and Drug Administration, said the watchdog agency didn’t have a problem in principle with prescription manufacturers developing both opioids and overdose antidotes. “These are very large companies that manufacture many, many drugs,” he said, “so it doesn’t appear unusual that they make both fentanyl and naloxone.”

Naloxone products

Nasal spray

Adapt Pharma

Injection

Eurohlth Intl Sarl

Hospira

Intl Medication (Amphastar)

Mylan institutional

Auto-Injector

Kaleo Inc

Source: U.S. Food and Drug Administration (FDA)

‘It’s truly a lifesaver’

No one disputes that naloxone is really, really good at what it does, and what it does is save lives. First approved by the FDA in 1971 and available in generic form for several decades, it’s relatively inexpensive by itself. But to deliver it quickly to overdosing drug users, pharmaceutical companies have patented various naloxone delivery-systems -- from subcutaneous shots to a nasal spray. These apparatuses have proven particularly valuable to emergency first responders -- and especially lucrative to manufacturers.

One dose of the drug can wake a victim up within minutes. It has reversed more than 26,000 overdoses between 1996 and 2014, according to the Centers for Disease Control and Prevention. Data provided to Fusion by 12 fire and police departments show that those agencies’ responders used the drug to revive at least 2,090 people from overdoses since 2010.

“It’s truly a lifesaver. There is no doubt in my mind that at least 50 percent of our reversals would have been fatal had the officers not responded with naloxone,” said Quincy, Massachusetts, police Lt. Patrick Glynn. His department even keeps extra Narcan on hand to give to K-9 dogs in the event that they might overdose after sniffing narcotics.

For Kevin Doherty, a veteran firefighter at the Revere Fire Department in Massachusetts, just outside Boston, there’s deeper significance in keeping Narcan in stock. “It’s not just overdose calls,” he said. “It’s people in our community who we grew up with. It’s friends, it’s our coworkers’ friends and families. It’s become a piece of emotion along with every call.”

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Massachusetts’ Plymouth County Fire Department, farther down the coast, started carrying naloxone in February 2014. “When I bought Narcan for the first time, I thought, ‘I have so many that I’m pretty sure a lot of them will expire and I have to throw them away,’” said Chief Edward Bradley, who oversees the county’s seven fire stations. “But we were using Narcan as we were buying. There was a point that I didn’t have enough.”

Plymouth County alone had 106 overdose-related deaths in 2014 - one of the highest tallies in a state ravaged by heroin and fentanyl addiction, according to the Massachusetts Department of Public Health. “Using naloxone has become almost an everyday occurrence,” Bradley said.

In March 2014, just a month after Plymouth Fire got its first stock of the drug, Massachusetts Gov. Deval Patrick declared a public health emergency and took measures to make Narcan available to first responders, police officers and family members of drug users. By late 2015, all but a handful of states had enacted similar guidelines to increase naloxone access. CVS now sells naloxone over the counter to those who might need it in an emergency.

‘The pharmaceutical companies should be the ones paying’

But some first responders are conflicted about paying opioid-producing companies for overdose remedies -- especially as those emergency technicians see the price of Narcan skyrocketing. In Plymouth County, the price of a dose went up from $18.50 to $44 in just one month, according to Bradley. By October 2015, new doses cost the fire department $66.70 -- a 261 percent increase from the initial price.

“I thought: ‘It doesn’t make sense.’ It’s the same drug with the same label and the same expiration day,” Bradley, the Plymouth chief, said.

Plymouth Fire Department was not alone. In Ocean County, New Jersey, a $25 dose became $100 in a matter of months, according to the Fusion survey. In the Atlanta and Dayton, Ohio, police departments, prices doubled. The West Palm Beach Fire Rescue said they saw an 75 percent price increase in a year and half.

“It was going up from 20 to 40 to 60 to 70 dollars all within a relatively short amount of time, and that meant that our first responders in towns and cities had difficulty purchasing it because it was so expensive,” said Massachusetts Attorney General Maura Healey.

Naloxone price increase

There was an average price increase of 121 percent in the departments surveyed. All but two departments experienced such increase between 2014-2015. The list includes different Naloxone products.

According to a report by the Food and Drug Administration, two key naloxone manufacturers, Amphastar and Hospira, increased prices by at least 50 percent in 2014 nationwide. The American Society of Addiction Medicine attributed 29,000 deaths to opioid overdoses that year.

In August 2014, Healey entered into an agreement with Amphastar that resulted in lower prices for Narcan in Massachusetts. Since then, officials in at least five other states have negotiated similar deals with the company. Under New York’s contract, Amphastar offers a $6 rebate on every naloxone injection purchased. (Amphastar did not respond to Fusion’s repeated requests for comment.)

In January 2015, shortly before Hillary Clinton left its board of directors to run for president, the Clinton Foundation announced a major agreement with Kaléo Pharma, producers of the highly popular Evzio naloxone injector kit. Kaléo agreed to offer Evzio kits at a discount to colleges and emergency responders -- what former President Bill Clinton called “a more predictable and affordable pricing arrangement.” The subsidized costs were not disclosed; Evzio, which was approved by the FDA in 2014, can cost about $400 a dose, far more than some single-use naloxone products. (The Evzio dispenser contains two doses and typically retails for $800.) Vice has called it a “golden goose” for Kaléo.

A Clinton Foundation representative declined to specify the price that the organization and Kaléo negotiated for Evzio, but said that it was in ongoing talks “with multiple pharmaceutical companies” that produce naloxone. When asked about Evzio’s high cost, Kaléo spokesperson Mark Herzog told Fusion that “three out of four insured Americans” are covered for Evzio and that the median out of pocket cost for a box of two auto-injectors is $20. He also cited the donations the company has made to more than 200 organizations, including police and fire departments.

Revere Fire Department Chief Eugene Doherty called the drugmakers’ discounts a “pittance” compared with revenues the drugs generate -- and the responsibility he thinks they bear for the addiction crisis his firefighters battle daily.

“They're manufacturing the pharmacy drugs that these people are taking, and on the other hand they're marketing their Narcan. They are making money on both ends,” he said. “There should be a tax on them...the pharmaceutical companies should be the ones paying for all these recoveries.”

Dr. Lynn Webster, former president and spokesperson of the American Academy of Pain Medicine, told Fusion that accusing companies of intentionally creating addiction and profiting from it is “ludicrous,” he said. “The heroin is sold by cartels, not by the pharmaceutical companies.”

Naloxone average price

The list includes different Naloxone products.

‘Hospira wanted to increase the average customer bill’

2014 wasn’t the first time the pharmaceutical industry profited richly from naloxone during a crisis. Hospira, for years the primary distributor of the drug, increased its price by 1,100 percent in 2008—the same year that opioid overdoses were declared an "epidemic" by the Centers for Disease Control.

Dan Bigg, director of a major dispensary in Chicago for addicts, told Alternet in 2013 that when he approached Hospira for a discount, the company offered him a quick and dirty primer on its bottom-line decisions. “One of Hospira’s marketing executives explained the rationale behind the increase,” Bigg said. “He told me that Hospira wanted to increase the average customer bill by 3 to 4 percent. Instead of raising all their prices and risk losing customers to the competition, they combed through their list of products and chose one item for a price increase so high as to cause the average bill to go up 3 to 4 percent.”

Hospira didn’t directly address those allegations when asked about them by Fusion. “As organizations who have worked with Hospira over the years will attest, Hospira has responsibly priced Naloxone,” the company said in an email, adding that its actions “reflected sensitivity to the need for the product and constraints of community-based organizations, but also take into account the reality and necessary investments needed to produce high-quality generic drugs.”

Naloxone producers are also encouraging the “co-prescription” of naloxone to patients who are currently taking opioids and have a high risk of addiction. Kaléo, the producer of Evzio, has lobbied Congress on two bills that would have created a federal grant program to help pay for more naloxone co-prescriptions with opioids. (The bills are stuck in committees.) When asked about this two-for-one prescription approach, Herzog, the Kaléo spokesman, didn’t comment directly; instead, he sent Fusion reporters an article by the American Medical Association that describes co-prescribing medications as a "critical part of the solution" to the rising epidemic of opioid-overdose deaths.

Kolodny said co-prescribing “makes sense” in some cases, but it sidesteps larger ethical issues. “If a doctor is concerned that their patient is going to overdose, they should reconsider giving that patient high doses of opioids,” he said. “To some extent, if your patient needs an antidote for an overdose, why is the doctor prescribing such a deadly dose?”

Nevertheless, prescribing naloxone as part of a twofer to patients who take painkillers is gaining popularity. Webster, the American Academy of Pain Medicine spokesperson, thinks co-prescribing is a good idea: "It's all about the patient's safety."

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But it’s unclear whether AAPM’s pharmaceutical recommendations are sound medical advice, free of conflict. Records gathered under ProPublica’s Dollars for Docs database show that between August 2013 and December 2014, five doctors on AAPM’s board received nearly $800,000 in payments from prescription painkiller producers, including controversial makers of addictive fentanyl products like INSYS Therapeutics. The payments were for diverse reasons promotional talks, business consulting, honoraria, travel expenses, and gifts.

Webster was one of those doctors: He pulled in more than $65,000 from drugmakers. INSYS was his largest donor, giving him $8,642 for consulting, promotion, and travel expenses. Asked about those payments, he said that cooperation was “necessary” between the medical community and the pharmaceutical industry: “We need to work together to find solutions that are effective for public safety well-being and doesn’t ignore the needs of people in pain.”

Webster also had his clinic raided by the DEA in 2010. The agency concluded its investigation in 2013 without charges. Asked about the investigation by Fusion, Webster replied, “No comment. That’s history.”

AAPM’s non-profit foundation also lists five pharmaceutical companies among its top-contributing “Industry Founders Society Members.” Of those, four have produced naloxone or closely related “opioid antagonist” drugs. They include Purdue, the maker of Oxycontin, which faces ongoing scrutiny for its past marketing of opioids; in 2007, the company paid out one of the largest pharmaceutical fines in history, $600 million, after three executives pleaded guilty to falsely marketing the moneymaking painkiller as non-addictive and less harmful than it really is.

When asked about AAPM’s possible conflict of interest, Webster told us: “Everybody has a right to say what they think. I don’t believe any relationship with the industry has influenced our decision-making or created any bias.”

A high-priced Band-Aid, not a cure

To the extent that government officials are hanging their new drug-war hopes on naloxone, there’s a problem: The antidote saves lives, but it doesn’t stop addiction to heroin or prescription painkillers. “We have better access to naloxone in the United States than in any other part of the world, and our overdose deaths are still far, far higher,” Kolodny said. In fact, overdoses reached record highs between 2014 and 2015, the years when naloxone went mainstream.

“You are saving a life only in that moment. Everyone who reverses most likely will reverse again and again,” said Connie Green, who pioneered a program in New Jersey that connects drug users with rehab and detox centers when they are taken to the state’s emergency rooms. “That’s the story of addiction. As you get into it, your tolerance increases, and so does the use. We are seeing repeated Narcan reversals all the time.”

If politicians and pharmaceutical companies were serious about stemming the addiction epidemic, Kolodny said, they would address prescription opioids directly. But “there is a contradictory message within the Obama administration,” he said. “The CDC is saying doctors need to prescribe more cautiously. President Obama is saying doctors are overprescribing. And yet the FDA keeps approving new pills, new painkillers.” He noted that federal officials approved Purdue Pharma’s Oxycontin for use by children last year.

Pahon, the FDA spokesperson, said his agency faced a “balancing act” between providing needed medications and tamping down on abuse and overdoses. “A car could be dangerous, but you don’t stop car manufacturers from putting in seatbelts,” he said. “Naloxone is the seatbelt. This is a safety measure, and it is saving lives.”

Shrinking the supply of addictive painkillers is an unglamorous strategy. It’s easy to see the lives that naloxone saves, and it’s hard to put a ceiling price on saving a life, as pharmaceutical companies well know. From a bottom-line perspective, repeated naloxone use is good business.

David Harak, the recovering addict and veteran of several naloxone revivals, gets that. He said his experience suggests hardcore users will need ever more antidote, as surely as they need more fixes.

“It's taking multiple Narcans now to wake somebody up,” he said. “So it's money, money, money.”