Ready access to opioid antagonists such as naloxone can make all the difference during an overdose. Now, the FDA is chipping away at one of the chief impediments keeping the potentially lifesaving drugs out of reach.
In a Federal Register notice issued (PDF) Tuesday, the U.S. drug regulator released its preliminary assessment that certain naloxone products “may be approvable”—i.e., safe and effective—for over-the-counter use. The decision—while not a formal OTC approval determination—is many years in the making and could ease development and approval of nonprescription naloxone, the agency said in a release. This could include transforming the approvals for existing prescription naloxone products into OTC nods.
The OTC endorsement specifically covers naloxone nasal spray and intramuscular autoinjector delivery formats up to 4 mg and 2 mg, respectively. The FDA singled out two “community-use” naloxone products—Kaleo’s prefilled autoinjector Evzio and Emergent BioSolutions' nasal spray Narcan—as prime candidates to “inform the public health decisions for layperson use.”
At a naloxone access workshop in March, Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research, noted that injectable naloxone is the cheapest form of the medicine, though its vial and syringe format “poses particular challenges for OTC development.” OTC drugs need to be usable by the public without healthcare professional supervision, including by people who’ve never injected a medication.
Whether delivered through a needle or the nose, all current naloxone meds are prescription products. That said, all 50 states have access laws allowing pharmacists to dispense naloxone without a doctor’s prescription.
Despite those laws, access barriers persist, the FDA pointed out in its notice. According to a preliminary review by the agency, “knowledge gaps” surrounding state-level naloxone access laws may be keeping certain pharmacies from dispensing the drugs.
The agency has flagged other more existential issues, too, such as the persistent stigma that surrounds addiction and substance use disorders.
Before the FDA can make a final call on the fate of OTC naloxone, the agency needs additional data and details, such as product-specific packaging and label design for potential OTC presentations.
When it comes to higher doses of the drug, plus other formats such as vials, ampules or syringes without integrated needles, the FDA will need to parse through additional safety and efficacy data, too.
Loosening the opioid crisis’s grip on the nation has been a key item on the federal health agenda lately. Back in September, President Joe Biden made beating the epidemic a key pillar of his agenda in his first State of the Union address.
Alongside more than $1.5 billion in total federal funding to support substance use treatment and prevention, Biden’s plan included new FDA guidance meant to ease distribution of approved naloxone with a specific focus on boosting access in underserved communities.
The FDA’s preliminary OTC proclamation is just one of many changes taking place within the overdose reversal drug scene. For starters, Teva Pharmaceutical and Novartis’ Sandoz unit last December launched separate copycat versions of Emergent's Narcan.
Emergent had been paying a royalty to Opiant Pharmaceuticals linked to certain Narcan formulation patents, but that arrangement has ended, an Emergent spokesperson said via email.
Speaking of Opiant, the company is nearing the finish line with another nasal spray prospect called nalmefene, which Opiant suggests may work better than naloxone at treating overdoses on synthetic opioids like fentanyl. The company aims to finish a rolling submission for that drug to the FDA by year-end.
Seemingly enthused by the prospect of that approval, Indivior just this week agreed to pay $20 a share for the opioid antagonist developer, resulting in a $145 million upfront buyout fee, plus another $8 per share to follow if certain sales targets are met.
Editor’s note: This story has been updated to correctly state that Emergent BioSolutions owns Narcan, not Opiant Pharmaceuticals.