Navigate the naloxone economy

In June, North Carolina joined the short list of states to issue a standing order for any pharmacy to provide the overdose reversal drug naloxone without a prescription. The order was signed by Gov. Pat McCrory as part of an effort address the state’s growing opioid overdose problem. That same week, drug store chain Walgreens announced it was making naloxone available without a prescription in all of its pharmacies in several large states.

Those are just the latest among efforts to increase access to the drug, which can revive an overdose victim in seconds. However, the rising cost of the drug in some forms might make it more difficult for those efforts to be successful.

The drug and the delivery

Naloxone was initially approved by the Food and Drug Administration (FDA) in 1971, and the molecular entity has long since lost its patent. However, new patented delivery mechanisms are changing the proposition for its use.

For decades, naloxone was administered by using a hypodermic needle. However, naloxone in self-contained, nasal-spray delivery packaging (branded as Narcan from Adapt Pharma) was approved by FDA late last year. The new mechanism makes it easier for users without medical training to administer the drug—an important innovation, as the drug is increasingly being provided to laypeople.

In addition to the Narcan nasal spray product and the traditional injectable version, there is also an auto-injector version approved in 2014 (Evzio, from Kaléo) as well as kits that combine the syringe with a twist-on atomizer to create a nasal spray (from several manufacturers) that have been used by first responders for years but are not specifically FDA approved.

Ease of use

Simpler delivery mechanisms are making it easier for laypeople to administer the medication in an emergency. Seabrook House, a treatment provider based in Seabrook, N.J., is providing Evzio prescriptions to all of its patients with opiate use disorder histories upon discharge. According to medical director Joseph Ranieri, ease of use was critical.

“Even at our own facility, I’ve seen staff struggle or fumble with the generic syringe version,” Ranieri says. “You have to screw the vial on the syringe. If you use the intranasal version, you have to get [the patient] on their back and attach the applicator. It’s difficult even for medial professionals. With the injector, you open it up and put it on their leg.”

Efforts to increase access to naloxone are having an impact. In June, New Mexico’s State Department of Health announced that the number of drug overdose deaths had decreased by 9% over the past year, thanks in part to legislation that made it easier for community-based programs and first responders to obtain the drug.

The good news is just about anyone can administer naloxone today. A recent study conducted by researchers from the National Institute on Drug Abuse (NIDA) and the National Institutes of Health (NIH) compared the efficacy of intranasal naloxone to the higher dose delivered with the intramuscular injection, and found that not only was the nasal spray version potentially more effective, but that it was easier to administer with no prior training.

However, price increases have community organizations, first responders, healthcare providers and state governments up in arms.

The Harm Reduction Coalition says that generic naloxone in a syringe cost roughly $1 per injection 10 years ago, but that has increased to up to $30 per dose today. Amphastar’s prices for its naloxone kit doubled to about $50 in 2015, while the Evzio auto-injector can cost as much as several hundred dollars per dose or more. The Narcan nasal spray is new to the market without historical cost data, but lists for $125 for two doses.

Challenge for state programs

Price increases across the market are proving to be a challenge for states and organizations trying to expand access to the drug in the communities where it’s most needed. And demand is rising.

“We’ve heard that some providers have seen a 17-times increase in the past two years as the drug increases in popularity,” says Kent Runyon, vice president of community relations and chief strategist and compliance officer for Novus Medical Detox Center. “Prices have not gone down as production has increased. That is disappointing given the nature of the medication and the importance of it to the overdose problem.”

Few doubt the usefulness of the drug and its newest delivery mechanisms, but some wish the pharmaceutical manufacturers would reconsider pricing structures.

“The industry as a whole is not acting in bad faith or exploitatively, but I do think there are some members of the pharmaceutical industry that are making bad commercial decisions, and they should consider the public interest and, frankly, their own public relations,” says Michael Barnes, executive director for the Center for Lawful Access and Abuse Deterrence (CLAAD).

Complicating matters, he says, are the number of third-party repackagers creating what are essentially unapproved kits with the naloxone syringes.

Barnes adds that some manufacturers are scaling their prices up to match the price of new delivery systems. For example, after the introduction of the Evzio auto-injector (which includes an electronic audio system that provides step-by-step instructions), Amphastar increased its prices for a 10-pack of 2mL syringes by nearly 60%.

“That should create an opportunity for generic manufacturers,” Barnes says.

In the meantime, there’s a lot of money to be made in naloxone. In the first quarter of 2016, Amphastar reported that naloxone sales increased from $6.7 million in the first quarter of 2015 to $10.3 million in 2016. Last year, it had attributed that growth to both increased unit volumes and higher average prices.

Additional entrants could help increase competition and lower prices. Amphastar has filed an application for its own intranasal packaging of naloxone. A third company, Indivior, was also seeking approval for naloxone nasal spray, but its application was rejected.

States take manufacturers to task

In response to complaints, manufacturers have begun rolling out rebate programs and no-cost supplies for certain organizations—a strategy they also use with other stakeholders and drug classes. Adapt Pharma is providing free cartons of Narcan nasal spray to high schools, for example.

The Evzio auto-injector is available with a zero copay card as well. That offer is what drew Seabrook House in New Jersey to the product. Seabrook is working with a specific contract pharmacy to ensure patients actually get the prescriptions filled while they are in treatment, as opposed to issuing a prescription at discharge, which has a greater risk for nonadherence.

“One of the reasons I picked Evzio was because of the zero copay,” Ranieri says. “If the copay were $60 or $100, a lot of patients wouldn’t make any attempt to get it filled.”

State attorney generals and some state legislators are also looking to address prices. So far, these efforts have largely resulted in settlements. Last year, the New York attorney general announced an agreement with Amphastar Pharmaceuticals to provide a $6 rebate per dose on the company’s naloxone kits for police departments and other agencies (the rebate was also provided to several other states). The company also agreed to increase the size of the rebate to match any rise in the wholesale price of naloxone for the following year.

Separately, Amphastar paid $325,000 to Massachusetts to provide access to naloxone via a discount program.

“If prices continue to increase, we will see that attorney generals and other consumer protection agencies will take additional aggressive action against the pharmaceutical industry,” Barnes says. “In our analysis of price-gouging laws, we found that they apply when there is an emergency. In the case of the opioid overdose epidemic, we have a public health emergency. Any companies that increase prices for purposes that are not justified by the market can be subject to prosecution under state price-gouging laws.”

Wider availability

Eventually, naloxone kits could be as common as the defibrillators found in schools, department stores and libraries.

“As more and more Americans recognize the impact of heroin and opioid abuse—and realize that people who are using these substances are everywhere—there will be a call for immediacy of response everywhere,” Barnes says. “We’ll see a wider presence of naloxone in homes and facilities.”

CLAAD’s position reflects that of the industry at-large, insisting that access to naloxone needs to be accompanied by education and programs to advance treatment. Those who need the resources of naloxone should get it from people who have their best interests and health in mind, Barnes says.

“Each time a life is saved with naloxone, it’s an opportunity for that person to make the decision to turn their life around,” Runyon says. “If this medication is in the hands of first responders and family members and it saves a life and gets them to our door, then it’s money well spent. The more hands it is in, the greater the capacity to save lives.”

The market for naloxone is likely going to increase and as more states pass laws and create standing orders that make it easier for first responders and the general public to access the drug:

• Naloxone can be offered behind the counter without a prescription in at least 14 states, and three states have statewide standing orders in place.
• Chain pharmacies like CVS and Walgreens are ramping up efforts to offer it in thousands of stores without a prescription, although there has been some confusion among pharmacies about the orders. Surveys by several Pennsylvania newspapers found many pharmacies either did not stock naloxone or believed it still required a prescription. The surveys also found varying prices up to $4,000.
• The Carlisle, Pa., school board in June adopted a new policy governing the use of naloxone on school district property. The district stocks naloxone at its high school and middle schools, where it can be administered by school nurses and other trained employees. The Pennsylvania Department of Health is encouraging all districts to adopt similar policies.
• In Berkshire County, Mass., the district attorney’s office provided a $17,000 grant to the local health system to stock naloxone.
• In Columbus, Ohio, fire departments spent $147,000 in 2015 delivering 2,250 naloxone doses, and now thanks to recent legislation, the capitol city has extended use to its 800 law enforcement officers as well.

At the federal level, this year, SAMHSA provided $12 million to states to increase the use of naloxone. President Obama’s budget also included new funding to address opioid abuse with increased access to naloxone access as part of the package.

Future outlook

As of this writing, Texas was set to issue a standing order for all pharmacies to naloxone without a prescription in August. Meanwhile, community and medical organizations have organized naloxone training at hospitals and public libraries, and other organizations are handing out free naloxone kits.

Runyon expects mounting public pressure will ultimately force the hand of pharmaceutical companies to roll back prices.

“People are talking about this in the presidential race,” Runyon says. “It’s getting national attention.”

Brian Albright is a freelance writer based in Columbus, Ohio.