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

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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

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.

Ends

Notes to Editor:

About the PRO-E2 study

PRO-E2 was designed to compare the risks of using NOMAC-E2 versus COC-LNG.^8,9 VTE is an uncommon but serious adverse event linked to the use of COCs.^10,11 COC-LNG was chosen as the comparator for the study as the COC associated with the lowest risk of VTE, according to treatment guidelines.¹²

The study, initiated by MSD and conducted by ZEG-Berlin, was required by the European Medicines Agency (EMA).⁸ A PASS is carried out after a medicine has been authorised to obtain further information on a medicine's safety, or to measure the effectiveness of risk- management measures.

The primary outcome was risk of VTE (specifically deep venous thrombosis of the lower extremities and pulmonary embolism).¹ The secondary outcomes of interest were: all VTE, arterial thromboembolisms, idiopathic VTE, summary of VTE results, depressive disorders, mood change, cholelithiasis, inflammatory bowel disease, effect on fertility (contraceptive failure and return to fertility), pregnancy outcomes, weight change, hepatobiliary disorders, and acne.²

PRO-E2 was initiated in 2014 (following a precursor study, CELINA, initiated in 2012) and closed in December 2020.⁸ The results reflect real world practice in over 101,000 women (equivalent to 144,901 woman-years data) from across Australia, Austria, Colombia, France, Germany, Hungary, Italy, Mexico, Poland, Russia, Spain, and Sweden.¹

About Zoely^® (NOMAC-E2)

NOMAC-E2 combines nomegestrol acetate [2.5mg] and 17β-estradiol [1.5mg]. NOMAC-E2 is the only monophasic contraceptive pill using body-identical 17B-estradiol. Nomegestrol acetate (NOMAC) is a highly selective progestogen derived from the naturally occurring hormone, progesterone.^3,4

MSD was exclusively licensed by Theramex to sell Zoely ^® in certain territories (other than the US and Canada) until January 2020 and held Marketing Authorisations for the product in the non-EU markets of such territory. In January 2020, these rights were transferred back to Theramex. The rights to sell the product in the United States and Canada pursuant to a license from Teva remained with MSD until the spin-off of Organon on June 2, 2021. Zoely^® and Stezza® are brand names of 2.5mg Nomegestrol Acetate NOMAC + 1.5mg 17β- estradiol E2 Combination Oral Contraception.

About Theramex

With a broad portfolio of innovative and established brands covering contraception, fertility, menopause and osteoporosis, we support women at every stage of their lives. Our commitment is to listen and understand our patients, serve their needs, and offer healthcare solutions to help improve their lives. Our vision is to be a lifetime partner for women and the healthcare professionals who treat them, by providing innovative and effective solutions that care for and support women as they advance through each stage of their lives. www.theramex.com

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
3. Theramex. (2021) Zoely^® SmPC. Available from: https://www.medicines.org.uk/emc/product/3038/smpc. Accessed October 2021
4. Westhoff C et al. ObstetGynecol 2012; 119(5):989-99.
5. Christin-MaitreS et al. Womens Health (Lond) 2013; 9(1): 13-23.
6. Van Vliet HAAM, Raps M. Cochrane Database Syst Rev 2011;(11): CD009038.
7. Duijkers IJM et al. Eur J Contracept Reprod Health Care 2010; 15(5): 314-25.
8. Clinicaltrials.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 Saf. 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: www.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): CD010813.
12. Faculty of Sexual & Reproductive Healthcare. FSRH Guideline Combined Oral Contraception. January 2019 (Amended November 2020).

*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

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Contact information

Andrew Bradley, Head of Communications, Theramex
andrew.bradley@theramex.com / +44(0) 7864 167962

Donna Gregory / Makara Health
donna@makarahealth.com / +44(0) 7917 912 271