I subscribe to The Medical Letter to learn about new drugs. I am frequently appalled by their cost. For example, a year’s treatment with Ozanimod, a drug recently approved for multiple sclerosis, costs $84,800. And some new drugs cost much, much more than that. A gene therapy drug from Novartis currently holds the record: 2.1 million dollars for a year’s treatment. But in the August 2020 issue of The Medical Letter, I read about a newly approved drug that appalled me for many other reasons. It simply made no sense.
Many types of contraceptive are available; the most effective are intrauterine devices (IUDs) and the etonogestrel implant, both with a failure rate of 0.1%. Even sterilization surgeries have worse failure rates (0.5% for tubal ligations, 0.15% for vasectomies).
Hormonal contraceptives (“the pill” and other versions including transdermal, injectable, and vaginal rings) generally have a failure rate of 0.3% with perfect use and 7% with typical use. Barrier methods like diaphragms, cervical caps, sponges, and condoms are much less effective. The failure rate of spermicides used alone is 16% with perfect use. The rhythm method of birth control was so ineffective it spawned this riddle: what do you call people who use the rhythm method? Answer: parents. But now the symptothermal method offers better odds: a 0.4% failure rate with perfect use.
Of course, the only 100% certain method of preventing pregnancy is my favorite method, orange juice. You may ask, “before or after?” The answer is “instead of.” My second favorite method is from a joke about a census taker who knocked on doors and asked what contraceptive methods people used. At one house, a very tall woman answered the door and said she relied on the saucer-and-bucket method. The census-taker had never heard of it, so he asked the woman to explain. She said, “You may have noticed that I am very tall; my husband is much shorter, so he has to stand on a bucket; when his eyes get as big as saucers, I kick the bucket out.”
Over-the-counter products containing the spermicide Nonoxynol-9 have long been available; there are many varieties including creams, foams, gels and suppositories. They can be used in combination with barrier methods and have both advantages (low cost, no need for a prescription or a visit to the doctor) and disadvantages (messy, must be used within an hour preceding each act of intercourse, do not protect against sexually transmitted diseases, may cause irritation, and may increase the risk of HIV transmission.
The FDA recently approved Phexxi (Evofem), a nonhormonal vaginal gel whose active ingredients are lactic acid, citric acid, and potassium bitartrate. It works by maintaining an acid pH in the vagina. It was approved on the basis of one single-arm trial (AMPOWER) of 1384 women. Its main competitor would seem to be the nonoxynol gel. How do the two compare?
They are similar on many counts. Both Phexxi and spermicide gels must be inserted in the vagina within an hour before each act of intercourse. Neither protects against sexually transmitted diseases. Both can cause irritation in both partners. Both cause increased lubrication.
But there are some important differences. Spermicide gels are available over-the-counter; Phexxi requires a prescription. Spermicides cost only pennies per use; Phexxi costs $267.50 for a box of 12 single-dose prefilled applicators, which works out to over $22 for each use. The estimated failure rate for Phexxi based on the AMPOWER study was 27.6 unwanted pregnancies per 100 woman-years of use, much higher than the estimate of a 16% failure rate for perfect use of spermicides and 21% for typical use.
What was the company thinking? As I was pondering this conundrum, I discovered a clue. The gel was previously approved by the FDA as a vaginal lubricant, Amphora, or Acidform. But they never actually marketed it as a lubricant. They had found some preliminary evidence that it might protect against sexually transmitted diseases, and I’m guessing they hoped they could market it with the claim that it offered this advantage over previously available products; but apparently further research didn’t pan out. So what to do? Why not repurpose their lubricant as a contraceptive?
I am still mystified. How could they hope to get customers to switch from their current contraceptive to Plexxi? The Medical Letter did report that in the clinical study, “some women reported improvements in the ability to maintain lubrication and in sexual satisfaction with use of Phexxi compared to their previous contraceptive method.” Since that was not an end-point of the study, it only amounts to unconfirmed subjective anecdotes and it really tells us nothing. And of course, they are not marketing it for lubrication or sexual satisfaction.
It seems to me this was a last-ditch effort to find an excuse to market a product that had failed to meet the company’s early expectations. I can’t imagine anyone choosing to exchange their current contraceptive for it. I wouldn’t invest in this company. I will be surprised if Plexxi turns out to be a commercial success. But then, I have been surprised before and will gladly change my mind if they come up with better evidence.
For now, this product just doesn’t make sense. It may have convinced the FDA, but it doesn’t convince me.
This article was originally published as a SkepDoc’s Corner column on the CSI website.