A $2 Billion Category, and Policy That Keeps Changing
Cadence OTC CEO Samantha Miller on why no company is paid to make contraception easier to get, what a consumer label has to carry, and the convenience stores that did what the pharmacy system stopped doing.
Two in five pregnancies in the United States are unintended, and that share has not moved in a decade.
Lauren Rossen, Brady Hamilton, Joyce Abma, Elizabeth Gregory and colleagues at the National Center for Health Statistics rebuilt the national estimate in Vital and Health Statistics Series 2, Number 201, published April 2023. The unintended share went from 43.3% in 2010 to 41.6% in 2019, or 2,293,000 pregnancies in that final year, against a Healthy People 2030 target of 36.5%. The authors flag that abortions are likely undercounted, with their imputed totals running about 15% below other sources, and the series stops at 2019.
The intervention most often named to move it has been sitting on the table since 2012. The American College of Obstetricians and Gynecologists asked the FDA to make oral contraceptives available without a prescription in Committee Opinion 544, published in Obstetrics & Gynecology that December, concluding the benefits outweighed the risks. The College restated it in Committee Opinion 788 in 2019.
The combined estrogen-progestin pill, the most frequently prescribed oral contraceptive in the country, is still prescription-only. Progestin-only pills, one of which went over the counter in 2023, are prescribed far less often and largely to women who are breastfeeding or cannot take a combined pill. Not because the FDA refused the rest, but because the FDA cannot start the process itself.
"New drugs generally start as Rx," Samantha Miller told The Luteal. "They don't need to remain prescription for their entire lives."
Miller is the co-founder and CEO of Cadence OTC, a public benefit corporation based in Oakland, California. She spent three decades in pharmaceuticals, beginning at UCSD and the Salk Institute and then working in small-pharma business development and licensing, which put her across the table from the executives who handle drug asset sales. She founded the company with Malcolm Potts, a reproductive scientist and professor of public health at UC Berkeley, and Nap Hosang, an ob-gyn and public health specialist. The company says its team includes people who have run Rx-to-OTC switches before, which is a small population.
Cadence sells a low-priced emergency contraceptive, a pregnancy test and a UTI relief kit. What it is pursuing is a first-in-class switch of the combined pill, under the brand name Zena. No other company is attempting that switch.
Moving a drug off prescription requires a sponsor that owns the innovator rights to an existing prescription product. Not a generic. Miller bought two such products from Pfizer in January 2016, at $1 million each. Ten years on, the work is still not finished.
"We've done about 30 different labels and about 40, 42 studies," she said.
That is what the decade consists of. Draft the consumer labeling, test it with consumers including low-literacy readers and adolescents down to age 12, take FDA input, redraft, test again. None of it is published. She confirmed it is not on the company's site and has not been reported anywhere.
She has said publicly that four companies worldwide hold rights suitable for the application. The sponsor does not even have to be a for-profit company, she noted, but it does have to own the asset.
Three of those four have not filed, and her explanation is about return rather than will. The pills are off patent, so there is no patent term to defend. And what a filer wins is narrower than what a filer spends.
"Once you do a first-in-class Rx to OTC switch, it opens up for the whole class to become over-the-counter," Miller said. "It's really just the first company that does it."
The protection is three years. Under the Hatch-Waxman Amendments, a sponsor that conducts new clinical investigations essential to a switch receives three years of marketing exclusivity, and the label comprehension, self-selection and actual use studies a switch requires are the studies that qualify. Competitors license, run their own trials, or wait. Perrigo has described that three-year window as the thing gating its own switch business in successive 10-K filings since 2000.
Three years of protection for ten years of work, after which the precedent and the labeling template are available to everyone.
"Pharmaceutical companies don't prioritize primary care products," Miller said. "They don't prioritize women's health products, and they don't prioritize OTC products."
The category they are declining is not small.
Kimberly Daniels and Joyce Abma reported in NCHS Data Brief 539, published August 2025, that 11.4% of the 74.9 million females ages 15 to 49 in the United States were using oral contraceptive pills in the month they were surveyed, which is about 8.5 million people. The survey's standard error on that figure puts the range at roughly 7.6 million to 9.5 million.
Priced at what an over-the-counter pill actually sells for today, Opill's $20 per month or $50 per three-month supply, that user base represents a category worth somewhere between $1.5 billion and $2.3 billion a year at retail.
The NSFG classifies women using more than one method by the most effective one, so pill users who also use a more effective method are counted elsewhere and the 8.5 million understates total pill use.
The survey does not separate combined from progestin-only pills. Opill's price is a progestin-only anchor and no combined-pill retail price exists yet. And most insured users currently pay nothing with a prescription under the Affordable Care Act, so this is the gross size of the category, not the revenue a switch would newly create. NCHS also cautions against comparing this release with earlier ones because the survey moved to a multimode design with lower response.
It is a category measured in billions, sitting behind a filing that four companies are entitled to make.
Matt Fisher and Kapil Rawal catalogued every switch on the FDA's list from January 2002 through August 2022 in Therapeutic Innovation & Regulatory Science and found 45, of which 6.6% were novel on ingredient, class and indication together, roughly one every 6.7 years.
Both authors are employed by or affiliated with Haleon, a consumer healthcare manufacturer with a commercial interest in switch policy, and the paper counts approvals rather than explaining the rate.
Thirty labels is the other half of the explanation, because on a nonprescription product the label is the entire clinical encounter. Everything a prescriber would cover in an appointment has to fit on a box, a back panel and an insert, and work for someone reading it in a store aisle with no one to ask.
Miller's objection is to the benchmark that work is measured against.
"The FDA has a perception that physicians give perfect information to their patients," she said, "and that anything less than perfect information is not as good."
She points to what surfaces in her own testing. "We have a lot of people in our studies that have been taking birth control for a long time that are learning new things about birth control from our materials," she said.
The materials are written for the person taking the pill, in formats a physician package insert was never built to use.
Then the requirements changed mid-program. On December 26, 2024 the FDA published its final rule creating the additional condition for nonprescription use, or ACNU, effective January 27, 2025. It covers drugs where labeling alone cannot get a consumer to the right self-selection, and lets a sponsor add a step such as a screening questionnaire or a digital label. Under 21 CFR 314.56 an ACNU product requires its own separate application.
The rule was written to widen access. The FDA's own program page states that no nonprescription drug with an ACNU has been approved.
"Oh yeah, they threw the ACNU at us," Miller said. "Halfway through, so we had to start over again at that point."
Manufacturing also has to be built to commercial scale with stability data, and cleared by the FDA, before the confirmatory actual use trial can begin.
Cadence has submitted the protocol for that trial and is waiting on clearance to proceed. She says the company is one of the three programs furthest along under the pathway, alongside one cardiovascular and one men's sexual health candidate, which is her account and was not independently confirmed.
"The more they increase their requirements, the more expensive it is, and the less happens," Miller said.
Her read on the current environment runs in both directions.
She flags the loss of senior agency staff as a live uncertainty, and credits the administration with pushing a reform agenda that includes increasing the number of first-in-class switches, the specific reform her decade of work depends on.
Ten years of that meant building a second business to fund the first.
"Given how long and expensive the first-in-class OTC switch project is, I needed some easier projects that I could get on the market quickly," Miller said.
"Most companies going through what we've gone through would not be surviving to continue today. It's really our innovations on the commercial side that have allowed us to." She says the company raised $45 million for the switch program, will need to raise again, and is profitable and self-supporting between studies. Those figures are company-stated.
Cadence sold into convenience stores rather than pharmacies, and treated that as a condition of launching at all.
"We're not going to launch our morning-after pill unless we had convenience stores on board," Miller said. "And so that's been our focus."
The reasoning is time. "These are products that you can't order from Amazon," she said. "You need to go get them immediately. Hours matter." Convenience stores are in every neighborhood, including the ones the pharmacy system is leaving. She credits one chain with opening the channel. "7-Eleven's been really innovative in stepping up and wanting to do it first. And then with that, we were able to get others to follow."
The company now reports being in more than 17,000 convenience stores across 49 states.
Rachel Wittenauer, Parth Shah, Jennifer Bacci and Andy Stergachis identified 4,679 census tracts as pharmacy deserts in Health Affairs Scholar in March 2024, 94.5% of which have no pharmacy at all. Of 60,475 community pharmacies nationally, 294 serve those communities. The count moves with the distance threshold used, and the study measures location rather than whether a prescription got filled.
Miller reads the decline as structural, pointing to a retail model under pressure and a falling number of pharmacists graduating, and notes those are often the same places without a gynecologist.
Clearing the FDA does not get a product onto a shelf. The three largest convenience chains carry the emergency contraceptive, along with many smaller ones. A large share of the rest do not.
"I would say half the convenience stores in the country won't carry it," Miller said. The estimate is hers from operating the category and was not independently verified. She describes two beliefs behind the refusals. One is that stocking the product encourages casual sex. The other is that emergency contraception ends a pregnancy rather than preventing one.
On the science she is unequivocal. If someone is already pregnant when they take it, "it will have zero effect on the implantation or viability."
Her explanation for why a factual error about how a drug works has survived two decades of over-the-counter sale is a market-structure argument, and it is the least familiar idea she offers.
Correcting a misconception at national scale costs money, and somebody has to have a reason to spend it.
For most of the category's history nobody did, because one seller and its private labels held the shelf.
"They haven't had to communicate or spread awareness or advertise because they had such dominant market share," Miller said. "So just having other companies out there advertising also forces them to use their voice more."
Competition, in her account, is what funds the correction. A second brand advertising forces the first to speak, and both have to explain what the product does. No public agency is running that campaign, and the FY2027 Title X priorities point the other way.
The information gap is not being closed by policy. It is being closed, slowly, by whoever decides marketing is worth paying for.
Policy is not correcting it. There is no federal requirement that private plans cover over-the-counter contraception without a prescription. Treasury, Labor and Health and Human Services proposed broadening that in 2023 and withdrew the proposal. Miller points to state action as the counterweight, and ten states now require certain state-regulated plans to cover some over-the-counter methods, according to the National Health Law Program's December 2024 count, though only six extend it to Medicaid enrollees.
Federal direction has moved the other way. The FY2027 Title X notice of funding opportunity, PA-FPH-27-001, published April 3, 2026, invites applicants to "reduce overmedicalization by strengthening approaches focused on underlying behavioral and lifestyle factors" of health, naming fertility-awareness-based methods as its example. Applications close January 9, 2027.
Miller says the anti-contraception conversation has not shown up in the numbers, and that prescription birth control volumes have not fallen. That is her read from inside the category rather than a dispensing figure.
Asked whether she still believes policy will not fix this, she did not soften it.
"We can't wait for policy to go our direction," she said. "I think we need to try to do something."
When asked what people building and investing in the category should be watching, she named three things.
None is waiting on a scientific breakthrough. Each is waiting on someone willing to fund the trial.
The first is vaginal estrogen. "Super important to get that over the counter," she said, "and nobody's, nobody's working on it as far as I know."
The timing on that is better than it has been in two decades. Low-dose vaginal estrogen, used for the genitourinary symptoms of menopause, has carried a boxed warning drawn from a trial of a different formulation at higher doses in older women. On November 10, 2025 the FDA announced it would remove the boxed warnings from hormone therapy products, and it has since approved the first labeling changes across four categories, including topical vaginal estrogen.
Twenty-nine companies submitted proposed revisions.
The warning that would have made a consumer-facing label close to unwritable is being taken off right now, and no sponsor has filed to switch the product.
The second is a study rather than a product. She wants to test the emergency contraceptive in the window immediately before sex rather than after, running from 12 hours prior up to immediately prior. "It should work better if you take it right before," she said.
The broader idea has a research history. A Phase III trial published in Human Reproduction in 2016 enrolled 330 women taking levonorgestrel 1.5 mg around the time of sex and found typical-use efficacy of 7.1 to 11.0 pregnancies per 100 woman-years, weaker than daily oral contraception.
An earlier study of a 0.75 mg dose in the United States and Brazil, published in Contraception in 2014, stopped after 72 of a planned 300 participants enrolled. A Cochrane review of repeated pre- and post-coital hormonal contraception found the pooled results promising and the underlying trials limited.
What those studies did not isolate is Miller's window. They allowed dosing up to 24 hours on either side of sex, which mixes the two uses together.
Current labeling covers only the use after sex, so the use before it cannot be promoted, and she was direct that the study would be expensive and hard to run.
The third is one she is watching rather than building. Male contraception, she says, would be a breakthrough for female contraceptionreal.
Her last argument is about what a switch is worth beyond the shelf. Once a drug goes over the counter, manufacturing and packaging stay tightly controlled. Sales and distribution do not.
"Whereas by prescription you can kind of lock something down with a new, you know, a new political move," she said. "You can't do that with OTC."
The FDA either clears the actual use trial protocol or it does not. If it clears, Cadence runs the last study a switch requires, and the application that ACOG asked for in 2012 finally exists. Three years of exclusivity follow, and then the class Miller has spent a decade opening becomes available to every company that declined to open it.
Four things determine whether a person can buy contraception in this country. Who owns the rights. Who pays for the studies. Who stocks the shelf. Who funds the information on the box. Policy sets none of them.
No other company is attempting the combined-pill switch.
Cadence owns the rights, is paying for the studies, and built the shelf space itself.