Safety results from large real-world safety study in combined oral contraception published

• The real world PRO-E2 safety study of over 101,000 women in 12 countries has confirmed that the risk of venous thromboembolism (VTE)^* is at least as low with Zoely▼^® (NOMAC-E2) as with levonorgestrel-containing combined oral contraceptives (COC-LNG)¹
• The study also demonstrated a statistically significant lower risk of unintended pregnancy compared with commonly prescribed COC-LNGs ²
• NOMAC-E2 is the only monophasic combined oral contraceptive (COC) to contain estrogen with an identical structure to the one naturally produced by women^3,4

LONDON, UK – 14 October 2021. Theramex, a global women’s health company, today announced that the safety results from the PRO-E2 real-world safety study for Zoely^® (NOMAC-E2) have been published in The European Journal of Contraception and Reproductive Health Care (EJCRH).¹

The post-authorisation safety study (PASS), known as PRO-E2, was a large, prospective, non-interventional controlled cohort study of over 101,000 women. PRO-E2 compared the risks of using NOMAC-E2 versus COCs containing levonorgestrel (COC-LNG), a commonly prescribed contraceptive.¹

The primary objective of the real-world study was to assess and compare the risk of cardiovascular events* in NOMAC-E2 users with COC-LNG users. For the main clinical outcome, the risk of VTE^† was as least     as low with NOMAC-E2 as with COC-LNG, consistent with findings of previous studies (0.59  Hazard Ratio [HR]† 95% confidence interval [CI], 0.25-1.35).¹

*Specifically deep venous thrombosis of the lower extremities and pulmonary embolism

†HR adjusted for age, body mass index, current duration of hormonal contraceptive use, family history of VTE

PRO-E2 also demonstrated that contraceptive failure (the risk of unintended pregnancy), a key secondary outcome, was statistically significantly lower with NOMAC-E2 compared with COC-LNG (0.45 HR†, 95% CI, 0.34-0.60, [p<0.0001]). Further analyses showed that the lower rate of unintended pregnancy with NOMAC-E2 was even more pronounced in women under 35 years of age.² The shorter hormone-free interval with NOMAC-E2, its longer half-life, and monophasic regimen may all contribute to fewer unintended pregnancies.^5,6,7  These results will be published in the EJCRH later this month.

All 14 secondary outcomes of the study were met, with the risk of severe adverse events and depressive disorders or changes in weight or acne score with NOMAC-E2 comparable to COC-LNG.²

Dr Joaquim Calaf Alsina, Honorary Professor of Obstetrics and Gynaecology at the Autonomous University of Barcelona, Spain, said: “This is an exciting real-world study which confirms what we suspected from both the biological profile and experience of using NOMAC-E2. This contraceptive combination has at least the same risk of VTE as the preparation shown to have the lowest risk in this aspect. The data from PRO-E2 also provides patients with important and reassuring data on efficacy and other added benefits, such as improvement of acne and low impact on body weight.”

Ms Claudine Domoney, Consultant Gynaecologist, Chelsea & Westminster Hospital, London, UK, said: “Contraception can be difficult for women and as clinicians we want to make it as easy as possible. In order to do this, there needs to be a range of options that offer reliable and convenient fertility control. The PRO-E2 study, which reflects the real-life experience of women, confirms that NOMAC-E2 is better at preventing unintended pregnancy than COC-LNG.”

Theramex CEO Robert Stewart said: “The PRO-E2 study results will build further confidence in what has already been shown to be a reliable and effective birth-control option. As a company dedicated to improving women’s health, we are delighted that the wealth of evidence from this safety study can help clinicians and women make informed decisions about contraception.”

The safety and efficacy publications were accepted by the EJCRH in September. The publication on safety results is available online:
https://www.tandfonline.com/doi/10.1080/13625187.2021.1987410

The efficacy publication will be available online later this month. Both publications will be available in the printed journal in December.

Results have also been submitted to the European Medicines Agency (EMA) and will be presented at the European Society of Gynecology congress in November this year.

References:

1. Reed S et al. Eur J Contracept Reprod Health Care. Available from: https://www.tandfonline.com/doi/10.1080/13625187.2021.1987410 Accessed October 2021
2. PRO-E2 final report. Available from: http://www.encepp.eu/encepp/openAttachment/studyResult/41498;jsessionid=uW82EciuLgcm015Qta9_pO v1_2skaG629DgRqfNG6I5-i02w5oS0!2052488890 Accessed October 2021
3. (2021) Zoely^® SmPC. Available from: https://www.medicines.org.uk/emc/product/3038/smpc. Accessed October 2021
4. Westhoff C et Obstet Gynecol 2012; 119(5): 989-99.
5. Christin-Maitre S et Womens Health (Lond) 2013; 9(1): 13-23.
6. Van Vliet HAAM, Raps M. Cochrane Database Syst Rev 2011; (11):
7. Duijkers IJM et Eur J Contracept Reprod Health Care 2010; 15(5): 314-25.
8. gov. (2021) Prospective Controlled Cohort Study on the Safety of a Monophasic Oral Contraceptive Containing Nomegestrol Acetate (2.5mg) and 17ß-estradiol (1.5mg) (PRO-E2). Available from: https://clinicaltrials.gov/ct2/show/study/NCT01650168 Accessed October 2021
9. Reed, S. et al. Pharmacoepidemiol Drug 2020;29 (Suppl.3):4.
10. US Food and Drug Administration. (2018). FDA Drug Safety Communication: Updated information about the risk of blood clots in women taking birth control pills containing drospirenone. Available from: fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-updated-information-about- risk-blood-clots-women-taking-birth-control. Accessed October 2021
11. de Bastos, M. et al. (2014) Cochrane Database Syst Rev (3):
12. Faculty of Sexual & Reproductive Healthcare. FSRH Guideline Combined Oral Contraception. January 2019 (Amended November 2020).