by Todd C. Frankel, Washington Post, 9/18/2023
Ainsley Bryce opens Narcan boxes in July in her office at Holler Harm Reduction, the clinic she runs in Marshall, N.C. (Mike Belleme for The Washington Post)
Five years after public health officials first asked for it, Narcan finally hit store shelves this month — a potentially pivotal moment in the fight to counter the country’s stubbornly high death toll from heroin, fentanyl and pain pills. Now, anyone can buy the opioid overdose reversal drug without a prescription.
But it almost didn’t happen.
Narcan’s maker, Emergent BioSolutions, for years refused to allow its blockbuster drug to be sold over the counter (known as OTC), frustrating health experts and workers on the epidemic’s front lines who saw making Narcan and other naloxone-based medicines easier to buy as a way to save lives.
“I’m not sure that OTC is the answer,” Daniel J. Abdun-Nabi, then Emergent’s top executive, told investors during a November 2018 earnings call. A month later, the company’s then president, Robert Kramer, cautioned “against a rush to an over-the-counter solution for this current crisis,” citing concerns about Narcan awareness and insurance coverage.
Robert Califf, head of the Food and Drug Administration, blamed Narcan’s over-the-counter delay on Emergent’s pursuit of profits. “I think the problem is that the financial model doesn’t appear to be working for the company, so they’re not motivated to do it,” Califf said at a 2022 conference. “We can’t order companies to go over-the-counter.”
Emergent’s reluctance ended in late 2022 after a competitor prepared its own bid for over-the-counter approval of naloxone, the wonder drug with the power to rescue overdose victims from the brink of death.
The move comes after the Gaithersburg, Md.-based company, along with Narcan’s previous owner, spent years appealing to the courts and regulators to stop other naloxone products from reaching the market and moved aggressively to lock up lucrative state contracts to supply the nation’s biggest customers — hindering broader distribution of the antidote while the opioid crisis worsened, according to interviews with more than 30 officials involved in naloxone distribution, as well as court transcripts and government and business records.
Emergent continued its campaign with corporate lobbyists who sat on government drug task forces in at least three states, seeking to raise its profile among decision-makers and potentially blurring the line between advocacy and sales.
No company has profited from naloxone like Emergent — despite the drug’s patent having expired three decades ago. The company recorded $1.4 billion in Narcan sales over the past four years. Its magenta-and-white Narcan nasal spray device has become a popular symbol used in public service ads and education campaigns.
“It’s a strategy that’s cost lives,” said Jennifer Plumb, a doctor and Democratic state senator in Salt Lake City who serves as medical director of the Utah naloxone program.
Emergent spokesman Matt Hartwig disputed that, saying that the company’s lobbying and government involvement are aimed at “raising awareness and expanding access” for both naloxone and Narcan, and that it will support the fight against the overdose epidemic “for as long as it is necessary.” He also said Emergent would not “speculate” about Califf’s comments from 2022.
The company has not charged eye-popping prices for its overdose reversal drug. Narcan’s list price hasn’t gone up since its debut in 2016. Public agencies got big discounts, too. A two-dose box of Narcan now sells for $44.99 over the counter at pharmacies and drugstores. Yet Narcan has long cost 10 times as much as other versions of naloxone — which cost as little as $2 a dose — fueling sporadic shortages as public interest organizations and local governments have struggled to pay for it. Last year, major harm-reduction groups in several states were forced to slash their Narcan distribution when they ran out of money to buy the antidote.
The debate over Narcan illustrates a central tension of the nation’s opioid epidemic response, with echoes of previous dilemmas over the distribution of AIDS drugs: How does society balance the almost limitless need for a vital drug with a private company’s desire to turn a profit?
The price of running out of Narcan
One example of Emergent’s corporate tactics was on display in the summer of 2021. Harm-reduction groups across the country were running low on naloxone because a major plant that produced the injectable naloxone that many of the groups preferred had temporarily shut down. Emergent, with its nasal Narcan, was among the last naloxone producers in the country.
In August 2021, three members of Remedy Alliance, a major nonprofit distributor of naloxone to harm-reduction groups nationwide, pleaded with Emergent officials for help.
Could Emergent donate Narcan to help with the shortage, the Remedy members asked during one phone call, according to two Remedy executives on the call and contemporaneous handwritten notes.
“They literally laughed at us and told us to not even put the request in writing,” recalled Nabarun Dasgupta, one of Remedy’s co-founders. “We were stunned.”
Hartwig said Emergent initiated the call, and “sought to provide solutions to help and never made light of this very serious situation.” He said company officials offered to help Remedy track down other naloxone supplies. Hartwig said Emergent has never donated to Remedy Alliance.
All of Emergent’s Narcan donations go through an unaffiliated charity, Direct Relief, which told The Washington Post that the company donated 28,056 doses in 2021 and 2022 — less than 1 percent of Narcan’s estimated production.
In comparison, Direct Relief said another naloxone producer, Pfizer, donated 951,880 doses during the same period. Pfizer said that amounted to about 20 percent of its production.
Days after the call with Emergent, Dasgupta, who also works as a senior scientist at the Injury Prevention Research Center at the University of North Carolina at Chapel Hill, estimated the naloxone shortage would result in at least 12,000 additional overdose deaths from opioids that year.
While it’s impossible to definitively connect the dots, the Centers for Disease Control and Prevention later reported that opioid overdose deaths had, in fact, increased by about 12,000 in 2021.
“People were rationing naloxone,” Dasgupta said. “And there was a cost to that.”
A fantastic molecule
Before Narcan, Emergent was best known for producing anthrax and smallpox vaccines for the country’s Strategic National Stockpile.
At the height of the covid pandemic, it made headlines for winning an emergency government contract to manufacture coronavirus vaccines. That deal ended in disaster when contamination concerns forced Emergent to trash at least 75 million doses.
Now, the company’s fate is closely tied to the opioid epidemic. Narcan accounted for 47 percent of Emergent’s revenue in the first half of this year, according to corporate filings.
The magic of Narcan is its active ingredient. Naloxone targets the same brain receptors as heroin and fentanyl, dislodging the chemicals that can slow breathing and starve the brain of oxygen.
Naloxone can be injected intramuscularly or sprayed into the nose. It acts with such precision and with so few side effects that instructors have been known to demonstrate how to use Narcan by giving themselves a dose.
Naloxone was discovered in the early 1960s. Hospitals have used it for decades. But today, as the opioid epidemic has spread into every corner of society, it is increasingly deployed by drug users, police, parents — even strangers on the street.
Two years ago, Julie Stampler saw a nurse performing CPR on a teenager who was passed out on a New York City subway platform. “He was essentially dead. No pulse. No breathing,” Stampler recalled. She always carried Narcan. Her stepfather, Jack Fishman, had co-discovered naloxone. And in 2003 her brother had died of a heroin overdose. Now, in the subway, Stampler used the naloxone nasal spray on the knocked-out teen.
“He got up and walked away,” she said.
It can be hard to imagine the scale of the nation’s opioid epidemic — which resulted in 80,000 fatal overdoses just last year — without naloxone.
Last year, in Allegheny County, which includes Pittsburgh, reported naloxone overdose reversals actually outnumbered opioid overdose deaths — 844 to 620, according to a county harm-reduction group.
“It’s a fantastic molecule,” said Traci Green, an epidemiologist who heads Brandeis University’s Opioid Policy Research Collaborative. “That’s why you need to get naloxone in as many hands as possible.”
The U.S. surgeon general has said everyone should carry naloxone.
The FDA has cut red tape to speed along new naloxone products — especially an over-the-counter version.
“The FDA has done more on this than any other drug,” said Joshua Sharfstein, a former agency deputy commissioner.
In 2012, the agency held a public meeting to get the pharmaceutical industry excited about the overdose treatment, taking a page from harm-reduction groups, which already were handing out liquid naloxone and syringes to drug users in Chicago and other cities. Naloxone was simple to use, especially for heroin users comfortable with a syringe. And injectable naloxone was inexpensive.
But the FDA wanted a product anyone could use without training.
The agency in 2014 approved Evzio, an auto-injector that worked like an EpiPen. But its price tag, which eventually hit $4,000, sank it.
About the same time, a tiny start-up called Lightlake Therapeutics, later renamed Opiant, had been testing a needle-free naloxone to treat eating disorders in Finland. That effort didn’t pan out. But now Opiant had a potential new market.
Federal health officials swooned over Opiant’s plan. They paid for early clinical trials and even suggested an off-the-shelf nasal atomizer to use in the product’s final design. Opiant officials were wary of launching a new product no longer protected by patent, according to court records. But they plowed ahead, and Opiant partnered with Adapt Pharma.
The FDA approved Adapt’s naloxone nasal spray in late 2015. Sales started a few months later.
The new product was called Narcan.
The name was already like the Kleenex of harm reduction: Narcan was the original brand name for liquid naloxone. Adapt capitalized on that and bought the rights to the famous name from Endo Pharmaceuticals, promising 2 percent of annual sales, according to information revealed in a patent lawsuit.
“Getting that name was brilliant,” said Maya Doe-Simkins, a veteran of harm-reduction efforts and a co-director of Remedy Alliance. “It was just built-in marketing and name recognition.”
Tapping into the Narcan market
Adapt Pharma then sought to fend off its competition.
It asked the FDA to require any generic competitor to meet a series of additional standards, including the production of new safety and chemistry data. The FDA mostly batted aside the technical requests. But the reviews took time.
A few months after Narcan hit the market, Adapt Pharma filed a patent infringement against the generic drugmaker Teva, which wanted to introduce its own naloxone nasal spray.
That lawsuit — which continued after Emergent acquired Adapt Pharma — ended up delaying Narcan’s generic competition by four years, until 2022. That’s when a federal appeals court upheld a ruling that Narcan’s patents were invalid because, as a federal district judge had found, Narcan’s success was less about its novel features than the “marketing strategies and tactics, and Narcan’s strategic pricing.”
Hartwig said Emergent had only “sought to lawfully protect its patent rights.”
Narcan had never been marketed like a traditional pharmaceutical, with doctor pitches and TV ads. Most of Narcan’s paying customers were in the “public interest market” — government agencies and nonprofits — according to the patent litigation.
That appealed to Emergent. Thanks to its vaccine business, it knew how to sell to governments.
In 2018, Emergent paid $735 million to buy Adapt Pharma and its prized product Narcan — the only drug Adapt made.
Emergent’s Abdun-Nabi praised the acquisition as “directly in line with our mission — to protect and enhance life.”
It was also a huge financial opportunity.
Government money for fighting the opioid epidemic — and buying naloxone — was just starting to flow. More than $2 billion in federal Substance Abuse and Mental Health Services Administration grants to fight opioid problems would go to states from 2017 to 2022. States, counties and cities then bought more naloxone with their own money, too.
Today, more than $50 billion in opioid lawsuit settlements is another huge funding source for naloxone on the state and local level.
Emergent has for years employed a small team of “state public affairs directors” to work with lawmakers “in educating them on the trends in their state and the importance of emergency treatment,” Eric Karas, an Emergent vice president at the time, testified in the Narcan patent lawsuit. Emergent also had a team of “field directors” to meet with state health officials and police, Karas said in court. Those teams helped Emergent secure contracts for Narcan, officials said.
Emergent lobbyists also pushed state politicians to draft laws making it easier to get naloxone. Every state eventually approved “standing orders” so anyone could get naloxone from a pharmacist without an individual prescription. Some states also passed laws encouraging doctors to co-prescribe naloxone with strong painkillers.
Some advocates welcomed Emergent’s help.
In Virginia, Emergent’s lobbyists pushed to streamline naloxone access, including for injectable naloxone, said Ginny Atwood Lovitt, executive director of the Chris Atwood Foundation, named after her brother, who died of an overdose in 2013.
“They helped us with that even though they knew we were going to be primarily giving out [injectable] naloxone,” Lovitt said.
But Emergent prioritized boosting Narcan sales. The drugmaker targeted state government grant writers, “creating a monthly scorecard of activities necessary to increase utilization of Narcan,” Michael Potestio, who at the time led the company’s field operations, testified in the patent case.
Emergent routinely met with health officials and community leaders “to share information about NARCAN Nasal Spray and better understand their needs in addressing the opioid overdose crisis,” Hartwig said.
Emergent staff members were involved in nearly every aspect of the effort to prevent opioid deaths. The company even managed to get its representatives on government working groups and committees where no other drugmakers did, including a 2021 strategic planning retreat for the Idaho Office of Drug Policy and a Michigan group that produced a plan for the state’s Opioid and Substance Use Disorder Task Force.
In Illinois, two Emergent employees sat on that state’s Opioid Crisis Response Advisory Council, where Emergent was joined by companies that included the makers of a drug to treat opioid addiction and another for related conditions.
“It is both constructive and common for people with expertise, which does include industry representatives, to engage with government officials to share best practices,” said Hartwig, the company spokesman.
Emergent’s efforts appeared to work.
Karas testified that Narcan controlled 75 percent of the public interest market for naloxone by late 2019, along with 97 percent of the consumer market.
Emergent declined to provide updated numbers.
A reality repeated across the country
While some advocates said they were pleased with the company’s lobbying help, others on the front lines of harm reduction felt compelled to use Narcan instead of less expensive injectable naloxone.
“There was lots of pressure on our organization and the state people about, ‘Do you know how many people are dying because you’re not buying these kits?’” said Plumb, the doctor in Utah, recalling her interactions with one Narcan field director.
She described it as “hardcore guilting.”
Plumb said she understood the appeal of needle-free naloxone, especially in a conservative state like Utah.
But Narcan was 10 to 20 times as expensive as the injectable form, Plumb said.
“They’ve done that thing where they try to present themselves as advocates,” Plumb said. “They are flat-out lobbyists.”
Harm-reduction groups said Emergent appeared to use its seats on government planning groups to push them to buy Narcan.
Doe-Simkins said she saw this happen in 2019 when she helped run the Chicago Recovery Alliance, among the oldest naloxone distributors in the nation.
State officials told the CRA it needed to spend 20 percent of its naloxone budget on Narcan, even though the group preferred injectable naloxone, Doe-Simkins said.
Emergent’s staff “was relentless with the state,” she said, and “they just told CRA they had to buy a certain amount.”
Harm-reduction groups couldn’t fight back, Doe-Simkins said.
“That reality is repeated all over the country,” she said.
Asked about the quota, an Illinois Department of Human Services spokeswoman said in a statement that service organizations “determine what formulation of naloxone is appropriate for the population and area of the state they serve.”
Hartwig said this incident appeared “to be an issue between [CRA] and the state.”
The problem is that there is often not enough money to buy sufficient Narcan to meet the surging need, said Joy Alonzo, a pharmacy professor at Texas A&M University who helps run the school’s opioid task force and gets naloxone from the state’s More Narcan Please program.
More Narcan Please has, at times, run out of Narcan, despite buying it at a discounted price.
“I have no particular allegiance to any of these companies” that manufacture naloxone, Alonzo said. “But their objectives are diametrically opposed to the medical community.”
Some of that pressure has recently abated. Narcan’s public interest price dropped from $75 per two-dose kit to just under $50 after generic nasal sprays finally hit the market last year. Now, the price has fallen to Narcan’s suggested retail price of just under $45.
Emergent dropped its opposition to a nonprescription Narcan in December.
That was after a small nonprofit drugmaker, Harm Reduction Therapeutics, revealed that it wanted to be the first company to seek the FDA’s greenlight. Emergent then filed its own OTC application with regulators.
“That was no coincidence. They could’ve filed at any time,” HRT co-founder Michael Hufford said. “But it was clever.”
Hartwig said HRT’s actions “had no impact on Emergent’s decision.”
Never enough Narcan
Narcan’s lifesaving role in the country’s opioid epidemic was on display earlier this year at a small clinic in Marshall, N.C., a mountain town outside Asheville.
Holler Harm Reduction provides drug users with clean “needles, cotton, cookers and ties,” along with Narcan and injectable naloxone.
Holler’s storefront sat between a DMV office and a county Republican headquarters. A truck parked outside boasted a “Holler if you need Narcan!” bumper sticker. Despite its out-of-the-way location, Holler handed out 1,700 naloxone kits last year, more than half of them Narcan. Those kits have helped reverse 156 overdoses reported to Holler since 2021, said Ainsley Bryce, who runs the clinic.
Bryce, who has worked in harm reduction for years, still marvels at the antidote’s power. In just a few gut-wrenching moments, an overdosed drug user goes from blue lips and dead weight to color in their face and breathing.
“It’s the coolest thing you’ve ever seen,” Bryce said.
Bryce sat at her desk and scrolled through a spreadsheet tracking the clinic’s naloxone supply. The column for Narcan had several gaps — September 2022, February 2023, among others.
“We keep running out of Narcan,” Bryce said.
It’s a simple calculation: Narcan’s higher cost, compared with injectable naloxone, means there is less to go around. Holler, run on a shoestring budget, relies on naloxone donated by government agencies and nonprofits.
“If we had to buy our own Narcan,” Bryce said, “we’d be screwed.”
By Todd Frankel
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