When life-saving medication should be in aisle three
By Tom Culman
As Engagement Associate at RA Capital Management, Tom Culman manages a variety of educational, outreach, and advocacy-oriented projects.
August 3, 2022
We talk a lot about access to care and the hurdles that might keep people from getting the medicine they need. Usually, we’re talking about the price of healthcare or the inanity of insurance requirements. But other hurdles hide in plain sight, as is the case with naloxone (Narcan), birth control, and other drugs that could (and should) be available over-the-counter (OTC).
Currently, bureaucratic and market forces stand in the way. One major problem is that while taking certain products OTC could have enormous benefits for public health, the financial upside for manufacturers is often minimal. But in the wake of the end of Roe, and with the first ever appeal to the FDA for OTC birth control, access to life-altering drugs are likely to become a hot-button issue yet again.
Abortion pills like mifepristone and misoprostol require a doctor’s prescription. (By the way: anyone can visit mayday.health for more information on how to get these pills discreetly mailed to you.) Levonorgestrel, the main ingredient in Plan B and other “morning-after” contraceptive pills, no longer requires a prescription, but it was a long road to get there.
Naloxone is a lifesaving medication designed to counteract the effects of a drug overdose within minutes. It’s available as a needle-free nasal spray and as an auto-injector, has minimal adverse effects, and won’t get you high if you attempt to abuse it. It’s also a prescription drug. And even though making other therapies available OTC has led to substantial rise in their use, manufacturers have done seemingly everything they can to make naloxone widely available except apply for OTC status. For the life of me I couldn’t come up with a good reason why, so I did a bit of digging.
I found the common themes between naloxone and levonorgestrel especially striking:
Both drugs are largely used by “at-risk” populations.
Both drugs are or have been available only “behind-the-counter,” rather than OTC.
Both drugs face social stigma.
“Behind-the-counter” in this case means that while you don’t need a prescription for the drug, there is some other restriction - most often age - that requires pharmacists to confirm that consumers are eligible to buy it.
When levonorgestrel was first approved for prescription use in 1999, its manufacturer applied for OTC status within four years. Conversely, naloxone was approved in 2014, but even with the FDA and lawmakers practically begging them to do so, manufacturers seem reluctant to apply for OTC status. Why?
Some Quick Background
It shouldn’t come as a surprise that the FDA is a bit cautious about approving drugs for OTC use. After all, if anyone can walk into a local pharmacy and buy a product, it has to be safe for as many people as is feasible. Specifically, OTC medicines must be safe enough for patients to use without a doctor’s guidance and must be for a condition that patients can reliably diagnose themselves.
At first glance, nasally-administered naloxone would seem to fit those requirements. But how confident are you that you could tell the difference between an overdose and a seizure, allergic reaction, or fainting spell? I know I wouldn’t want to bet anyone’s life on it. And luckily, with so few side effects, naloxone doesn’t ask you to. But this conundrum complicates its already-tough OTC approval process.
Part of the FDA’s process for determining whether a combination product that includes a device - like naloxone’s nasal injector - can be sold OTC is a “simulation,” formally called a human factors study. For something like naloxone, that might involve an actor simulating an overdose and a test subject charged with administering a placebo. The idea is to test the product in difficult situations, so those running the study might turn out the lights, turn on loud music, or have a second actor pretend to panic as a distraction. Human factors studies can be extensive and difficult. Scientists and manufacturers know how to plan for standard lab tests, but these simulations often fall outside of their usual purview.
Furthermore, to successfully apply for an “OTC switch” from prescription-only status, manufacturers are barred from altering the prescription product much. At most, a handful of drugs make the switch each year, mostly anti-allergens. Cadence Health is in talks with the FDA to take their birth control pills in this direction.
Products that require changes before going OTC, like levonorgestrel, must go through a totally separate “supplemental new drug application” (sNDA), a process that took developers about three years to push through for Plan B (plus an additional seven years for the drug to be available to all ages, but more on that below). The FDA approval process is complicated, expensive, and fraught.
Marketing & public perception
It’s clear that attempting to take a product OTC comes with a significant risk of rejection and bad press, which could hurt stock prices. So it’s hard to compel a company to take that risk, even though from a marketing perspective there’s supposedly no such thing as bad press.
Just like it was for levonorgestrel, public perception of Narcan is shaky. Any cynic might ask, “why should anyone be working so hard to save drug addicts when there’s cancer to cure and an ongoing pandemic?” That doesn’t make for a great reason to hold back OTC applications, but it is enough to give interested companies pause. No one wants to be seen as “the company for drug addicts,” especially if they would need to market themselves as such. Manufacturers of contraceptives have dealt with similar perception issues.
On top of the expense and risk of the application (whether for OTC switch or sNDA), launching an over-the-counter drug also requires a broad marketing campaign that targets a general audience, not just doctors and healthcare workers. Just think about all the ads you see for allergy medicines - the most common category of medicines to make the OTC switch. Only the largest manufacturers (or those partnered with them) have the money to advertise like that. And with little upside and potential backlash, many companies simply don’t have much motivation to do so.
Unless of course you can get free advertising from the news. The OTC approval of levonorgestrel was socially controversial enough for the FDA to ask for public comment before going through with it. (Of course they didn’t really need to ask; the public had plenty to say on both sides of the issue.) I’m sure there are those that would oppose naloxone going OTC, though I doubt (perhaps optimistically) that they would be as vocal as those who opposed levonorgestrel. So depending on your marketing strategy, that could be a pro or con.
But public pressure only goes so far. The FDA is on board, having already designed a consumer-friendly Drug Facts Label (DFL) so applicants won’t need to, but it’s ultimately up to naloxone companies to apply for it.
Behind-the-counter status diminishes financial upside
As it stands, in the US you can already get naloxone without a traditional prescription as long as you’re willing to jump through various hoops depending on the state you live in (and if you can find it in stock at a participating pharmacy). That’s great and makes the drug much more available, but these behind-the-counter programs still aren’t ideal for an emergency medication meant for some of our most vulnerable populations.
Levonorgestrel started in a similar but more familiar gray zone - when it first went OTC, you could get it at a pharmacy without a prescription, but needed to prove you’re over 17 to buy it. That’s a small hurdle we’ve largely grown to accept, but just because it works for drugs like pseudoephedrine (Sudafed) doesn’t make it a perfect compromise for contraceptives. Luckily, there is no longer an age restriction on most morning-after pills. It took a new formulation of levonorgestrel - Plan B One Step - and multiple sNDAs, but manufacturers eventually got the drug OTC status for all women.
Naloxone’s current status is far more restrictive than an 18+ limitation. No one can get the drug unless they did their research on state-wide distribution programs, have a prescription, or are lucky enough to get an unusually helpful and informed pharmacist. That means that most naloxone buyers aren’t recreational drug users, but bulk purchasers like hospitals, first responders, and nonprofits who would be largely unaffected by a switch from behind-the-counter to OTC. Any financial upside to making naloxone fully available OTC would be less than it would be if these otherwise lifesaving organizations and behind-the-counter programs weren’t around.
Manufacturers are quick to point out that making naloxone available OTC would lead to it being removed from many insurance formularies. This is a fair point, but seeing as the ACA carved out space for other OTC products to be covered (including emergency contraception like levonorgestrel), I’d hope we could do the same for something as important as anti-overdose medication.
Behind-the-counter availability also provides an excuse to any company that doesn’t want to take on the burden of taking naloxone OTC. They can simply point at existing programs and claim there is no remaining unmet need. But for a vulnerable population like drug users, even the flimsiest bureaucratic hurdle could prove enough to stand in the way of a product that could save lives. And as our post-Roe reality continues to unfold, OTC birth control might arrive just in time to save folks in dire need of contraceptives from the same heartbreaking situation.
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