Background
On April 15, 2015, the postcoital contraceptive ellaOne®, manufactured by HRA Pharma, became a prescription-free medicine, following a change in policy by the European Medicines Agency (EMA). The Spanish Association of Social Pharmacy (AEFAS) then requested a change in the information in the product’s package insert based on its mechanism of action, given the significant biases it allegedly contained.
EllaOne® is a medicine composed of the active ingredient ulipristal acetate. It is marketed as a postcoital contraceptive to be administered within 120 hours after unprotected sexual intercourse or when another contraceptive method fails.
As a selective progesterone receptor modulator, it modifies plasma levels of luteinizing hormone (LH), estradiol, and progesterone, which are highly involved in the menstrual cycle.
What does the EMA say?
The ellaOne® data sheet indicates that its only mechanism of action is the inhibition or delay of ovulation by suppressing the massive release of LH.
If its mechanism of action is the only one indicated, as the regulatory agencies maintain, this drug would only be effective before ovulation.
It does not possess, according to the EMA, any capacity to act subsequently by means of an anti-implantation mechanism that would cause the death of the early embryo.
AEFAS expressed its disagreement with this statement to the EMA, considering that it was not sufficiently scientifically supported. It sent a report on the change in the information in the summary of action mechanisms of ellaOne® to the EMA on October 10, 2012, and received a negative response in February 2013.
The change in the product data sheet referred to the removal of the information regarding its ability to cause changes in the endometrium, maintaining the inhibition or delay of ovulation as the sole mechanism of action. Based on various published studies, AEFAS claimed that ellaOne® induces changes in the endometrium that can result in embryonic loss, which would justify its efficacy.
New evidence supports its abortive effect
A recently published paper in the New England Journal of Medicine (NEJM) analyzes the efficacy of ulipristal as an abortive drug administered in the ninth week of gestation.
The current regimen for early medical abortion in many countries is mifepristone and misoprostol, but mifepristone is relatively expensive and limited in many regions, the authors note.
Ulipristal acetate, with a chemical profile similar to mifepristone, is now proposed as an alternative for chemical abortions. This study evaluated ulipristal acetate and misoprostol for medical abortion during the ninth week of gestation.
A two-stage clinical trial was conducted to select an effective and acceptable ulipristal-misoprostol regimen.
First, a dose-finding study was conducted. Sixty-six participants were randomly assigned to 60 mg or 90 mg of oral ulipristal, followed by 800 μg of buccal misoprostol.
Because the two groups had similar efficacy and safety profiles, the 60 mg ulipristal dose was selected for an open-label study with an additional 100 participants, resulting in a total of 133 participants using the same regimen. To assess acceptability, a structured questionnaire was administered at the end of the follow-up visit.
Side effects included chills (77.4%; 95% CI, 70.3% to 84.5%), diarrhea (66.9%; 95% CI, 59.0% to 74.8%), and nausea (48.1%; 95% CI, 39.7% to 56.5%). No serious adverse events were reported. The regimen was rated as “acceptable” or “very acceptable” by 97.7% (95% CI, 95.2% to 100.0%) of participants.
The study concludes that ulipristal acetate followed by misoprostol is an effective and acceptable chemical abortion option, with no serious adverse events reported.
Bioethical assessment
Following the publication of these results, will the EMA reconsider ulipristal’s mechanism of action, accepting its proven ability to cause embryonic death?
The International Federation of Gynecology and Obstetrics (FIGO) maintains the same position regarding denying the anti-implantation and abortive effects of ulipristal acetate. Will they now take this new evidence into account?
As we have previously published, this drug’s ability to block receptors for progesterone, the pregnancy hormone, explains its embryocidal activity.
As with levonorgestrel used for postcoital contraception, the anti-implantation effect, i.e., abortive in the strictest sense, is largely responsible for its effectiveness, an aspect that is also systematically denied by EMA and FIGO.
Hiding the mechanism of action of these drugs prevents potential users from making informed decisions about their use. This is especially true considering the possibility that these contraceptives may not prevent pregnancy, but, if pregnancy occurs, may end the life of the baby.
Behind this manipulation, inappropriate for international agencies and scientific societies that are expected to demonstrate scientific rigor in their positions, lies the tragedy of the loss of human lives. It also represents an attack on women’s autonomy and dignity, as they are prevented from freely choosing.
Julio Tudela
Director of Life Sciences Institute
Catholic University of Valencia
