In modern medicine, there are few drugs that can quickly reverse an otherwise fatal outcome. Naloxone is one of them.
For years — as the number of Americans dying from overdoses soared — advocates have been pleading to make this overdose antidote available over-the-counter (OTC). So why hasn’t it happened yet? We don’t know the answer to that, but one possible — and infuriating — reason: Because manufacturers producing the drug feared it would hurt their revenue.
The Food and Drug Administration only recently announced that it’s considering applications from two companies to make their naloxone OTC. To understand why it’s taken so long to get to this point, I spoke with Michael Hufford, the founder and CEO of one of those companies, Harm Reduction Therapeutics (HRT).
Hufford explained to me that FDA officials asked manufacturers to apply for OTC status at a conference in 2017. At the time, two naloxone products had been approved that were intended for layperson use. One was Evzio, an auto-injector modeled after the EpiPen, made by Kaléo. The other was Narcan Nasal Spray, made by Adapt Pharma, which has since been acquired by Emergent BioSolutions.
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Hufford, an addiction researcher who then worked in the pharmaceutical industry to take products from prescription to OTC, called each company to offer consulting support. “The companies told me that they had no intention to do this,” he told me.
That’s why he co-founded HRT as a nonprofit to manufacture naloxone. The other companies had already completed their clinical trials for the drug, but HRT had to start from scratch. It acquired and ran a clinical trial for a new intranasal formulation of naloxone. Then, it conducted a study to make sure consumers could use the product based on simple instructions. Finally, in October 2022, they finished submitting their application to the FDA.
“Within days of us announcing that we were going to submit our application, Emergent filed theirs,” Hufford said. “Unlike us, though, they could have done it years before. If they did, HRT wouldn’t have to exist.”
And that’s not for lack of trying on the FDA’s part. As HRT conducted its trials, the agency continued to urge the other companies to apply for OTC status. It even took the unprecedented step of creating a Drug Facts Label for naloxone. Such labels, which are the responsibility of companies, are required for OTC submission, and developing and testing them takes a lot of time and resources. The FDA even published the methodology for the label in the New England Journal of Medicine.
As Joshua Sharfstein, a former FDA principal deputy commissioner, told me, “The FDA rolled out the red carpet for applications to sell naloxone OTC by providing an easy path for companies to follow. Yet years passed without companies stepping forward.”
Why not? Hufford’s theory is that they made a conscious decision not to. “The fact is that they charge a significant premium because they get reimbursed for it as a prescription,” he said. “That’s a huge driver of margin and quarterly profits. From an economic standpoint, I get it. They were trying to maximize their revenues.”
I contacted both Kaléo and Emergent BioSolutions. A representative for Kaléo wrote that Evzio was discontinued in 2019. She did not explain why, but this came after a 2018 congressional investigation into Kaléo hiking Evzio’s price by more than 600 percent, from $575 per unit to $4,100. The company subsequently announced it would make a generic version available, at $178 per unit, then discontinued both the generic and brand-name versions.
Emergent’s president/CEO, Robert Kramer, said to me in an interview that he was “maybe not answering” my question about why the company delayed in seeking OTC status. But he assured me that “a lot of good work has been done” and that the “next logical step was going to OTC access.”
At the end of the day, I’m glad that both HRT’s and Emergent’s naloxone products are being reviewed by the FDA. Both are expected to receive OTC status as early as March.
But this long, drawn-out process raises important questions. For example, should the decision of OTC status be left solely to companies? Sharfstein thinks that the “FDA may need additional authority to make sure that safe, lifesaving medications are more readily available to people who need them.”
And, crucially, how will OTC naloxone be priced? It would be a terrible shame if one barrier to access were removed only to have another take its place.