麻豆传媒

Eliza Wheeler and several volunteers sit on the floor of her office and pack naloxone kits. They package up rubber gloves, rescue breathing masks, alcohol pads, and two atomizers.

And, of course, the key ingredient: two cartridges of nasal naloxone -- an old drug that can reverse an opioid overdose in seconds.

Wheeler and her team then distribute these kits free of charge to people in the San Francisco area who are at risk of or know someone at risk of an overdose.

It costs her organization, the , about $40 to make each kit. But that amount stands to rise sharply because Amphastar -- the lone producer of nasal naloxone in the U.S. -- will be doubling the drug's price starting Dec. 1.

The wholesale cost of each cartridge is set to jump from about $13 to $30, an increase that could make it hard for many nonprofit programs to distribute nasal naloxone, several of those groups told 麻豆传媒. Amphastar did not return calls for comment.

"The price increase does hurt these programs," said , director of substance use research at the San Francisco health department, and medical director of the , HRC's naloxone distribution program. "Many will have to switch formulations in order to stay afloat."

Demand Drives Price Increases

Injectable naloxone was first developed in the 1960s as an antidote to opioid overdose, and has long been an inexpensive generic. But a surge in abuse of prescription opioid painkillers and heroin -- in 2011, there were 16,917 prescription opioid deaths and 4,397 heroin overdose deaths, according to the CDC -- has boosted demand for the drug, once again making it attractive to pharmaceutical companies.

Hospira currently sells the lone injectable formulation. Generic drugmaker Mylan Pharmaceuticals said in March it would but it has not come to market yet, and the company did not return calls for comment.

Amphastar sells the only nasal formulation. The sole difference between the nasal and injectable forms is the concentration. The nasal version needs to be higher since it's not put directly into the bloodstream. It comes in a 1-mg/mL concentration, compared with 0.4 mg/mL for the injectable drug.

The latest formulation to hit the market is an auto-injector by Kaleo Pharmaceuticals called Evzio that was approved by the FDA in April and retails for around $700. (Kaleo executives declined to be interviewed for this article).

Heightened demand, a limited number of producers, and an expensive new product are a recipe for price increases, experts say.

"If someone comes on the market with a higher price, why would you not raise yours?" said , who specializes in drug abuse epidemiology at the University of Washington in Seattle.

Banta-Green is running a study of nasal naloxone, but is largely sheltered from the price increases because his work is funded by a National Institutes of Health grant.

That's not the case for organizations like Wheeler's. "Concern is coming from the community-based organizations who have tiny budgets," Banta-Green said. "More than doubling of the price is a big deal to them."

Community Groups Hit Hardest

Other advocacy groups affected by the price increase include , a nonprofit that distributes naloxone in North Carolina, and , a naloxone distribution pilot program in Virginia. Both aim to provide naloxone to "lay" users, or friends and family of those who abuse opioids.

Jason Lowe, project manager for Revive, said the price of nasal naloxone was a problem even before the impending increase. His organization is mandated by the state legislature to use nasal naloxone, but the group is not allowed to give it out directly. Instead, it gives lay users a prescription that has to be filled -- and paid for -- at the local pharmacy.

The retail charge has been $25 to $30 per dose, Lowe said, meaning the wholesale price doubling could saddle patients with an outlay of upwards of $120 for the two doses written in the prescription.

"We've already heard from our trainers that people in their communities have to choose between paying for naloxone and paying for clothes," Lowe told 麻豆传媒.

The markup may also pose a challenge to municipal budgets, as many first responders and police officers have started carrying nasal naloxone.

Indeed, New Jersey officials have , as the state launched pilot programs to equip first responders with the user-friendly drug last spring.

Costs Controlled by Few Companies

Most programs prefer to distribute nasal naloxone because the kits end up in the hands of friends and family of drug users who may not be comfortable handling needles. Groups distribute atomizers that must be attached to each cartridge of nasal naloxone in order to use it.

Studies have shown that nasal naloxone reduces overdose deaths when provided to friends and family of people at risk of overdose, including one done in Massachusetts and .

Nonprofits could save money by switching to injectable naloxone, which is cheaper but less user-friendly.

Wheeler, who is the , also sees that switch as a temporary solution to a much larger problem: that the cost of naloxone is controlled by only a handful of companies.

"You're being held at the whim of companies that can do what they want because they have a monopoly on a drug," she told 麻豆传媒. "The balance of our program rests on whether we can afford a product. That they can wantonly raise the price is terrifying."

Nonprofit groups historically have had some success when it comes to negotiating drug prices, particularly with regard to pricing of the injectable form. But many feel they are hitting a wall when it comes to the nasal version.

Lowe said some groups in his state have approached the Virginia attorney general with their concerns, but no action has yet been taken.

Fred Brason, CEO of Project Lazarus, questioned whether there was anything to prevent prices from simply continuing to rise.

Competition to the Rescue?

The groups are closely watching the development of a branded naloxone nasal spray, , and co-developed by Reckitt Benckiser, known in the opioid space for its addiction treatment drug buprenorphine (Suboxone).

Wermeling's company AntiOp announced in July that the FDA has granted its new drug application . It has not yet been okayed by the agency, and Wermeling did not provide an update on its progress.

If approved, his drug-device combo would be the only naloxone product indicated for nasal administration. Although Amphastar's nasal naloxone is made in the right concentration and without a needle attached, its use with an atomizer is technically off-label.

Lowe said he's hopeful that having an official indication for nasal naloxone would increase competition and potentially drive prices down. It may also boost insurance coverage, potentially making the drug affordable for more people. That would be a boon to his program, which sends patients to the pharmacy with a prescription.

Wermeling told 麻豆传媒 that the intention is indeed to have the drug covered by insurance and distributed through traditional healthcare financing routes -- as is the case with the auto-injector Evzio.

"It helps if you use traditional healthcare drug distribution and finance mechanisms," he said. "Programs that operate in harm reduction are not typically involved in that."

Different Models

That model doesn't help organizations like Wheeler's, which distribute the drug at no charge directly to users. They have to buy the product directly from manufacturers and are not shielded by insurers from price hikes.

Haggling with pharmaceutical companies over price "is not something any of us in the harm reduction community ever signed up for," Wheeler said.

She acknowledged that problem of rising costs is ubiquitous among generic drugs, an issue that has garnered much attention lately, most recently in the form of a Congressional hearing on generic price increases.

But Wheeler says the situation for nasal naloxone advocates is particularly frustrating: "Our model has been studied a lot, and we know it works, but it's really vulnerable to the market."

"For the past 20 years our model has been extremely effective in the distribution of the drug and training of laypeople," she added. "I'd hate to see 20 years of work dismantled."

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