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New Innovative Combined Oral Contraceptive Launched In The UK


Zoely ® (/17ß-estradiol) – new that contains an innovative combination of hormones launches in the UK

MSD (known as Merck in the United States and Canada) (NYSE:MRK) today announced that Zoely (nomegestrol acetate 2.5 mg/17ß-estradiol 1.5 mg) is now available in the UK for the prevention of pregnancy.

Nomegestrol acetate/17ß-estradiol (NOMAC/E2) is a combined oral contraceptive (COC) pill containing a monophasic combination of two hormones: nomegestrol acetate, a highly selective progesterone-derived progestogen that has a 46-hour half-life, and 17ß-estradiol, an oestrogen that is structurally identical to endogenous human 17ß-estradiol.[1] This innovative combination of contraceptive hormones is delivered through a 24-day active tablet and four-day placebo tablet dosing regimen.1

In a double-blind randomised clinical trial designed to investigate potential dosing regimens aged 18-38 years were randomised to receive either 24-day active NOMAC/E2 tablets with a 4-day placebo interval (n=40) or 21-day active NOMAC/E2 tablets with a 7-day placebo interval (n=37) over three cycles. The 24/4 NOMAC/E2 regimen was found to be associated with greater inhibition of follicular growth (largest mean follicle diameter: cycle 2: 24/4 regimen 9.0mm vs. 21/7 regimen 11.3mm, p=0.02; cycle 3: 24/4 regimen 9.2mm vs. 21/7 regimen 11.5mm, p=0.04) and a shorter duration of withdrawal bleeding (mean withdrawal bleeding duration after cycle 1: 24/4 regimen 3.5 days vs. 21/7 regimen 5 days, p=0.002; after cycle 2: 24/4 regimen 3.9 days vs. 21/7 regimen 4.8 days, p=0.03) than the 21/7 regimen.[2]

COCs are one of the most commonly used contraceptive methods in the UK.[3] A large review of national survey data in the USA reported that when contraceptive pills are used ‘perfectly’, as advised, 0.3% of women are estimated to experience an unintended pregnancy within the first year of use.[4] However, with typical use (actual use including inconsistent or incorrect use) 9% of women are estimated to conceive in the first year of pill use.4

Dr Diana Mansour, Consultant in Community Gynaecology and Reproductive Health Care, Head of Sexual Health Services, Newcastle Hospitals Community Health, Newcastle upon Tyne, UK, said: “The is still the most popular method used by women in the UK today. Women are always looking for choice and a method which provides effective contraception but with lighter and shorter periods sounds very attractive.”

Proven efficacy of NOMAC/E2

The efficacy and tolerability of NOMAC/E2 in a 24/4 regimen has been demonstrated in two randomised, open-label comparative trials in women aged 18-50 years.[5],[6] In the clinical trial performed in Europe, Asia and Australia, 1,591 women were randomised to receive NOMAC/E2 in a 24/4 regimen and 535 women randomised to receive a COC containing 3mg drospirenone and 30μg ethinylestradiol (DSRP/EE) in a 21/7 regimen for up to 13 cycles.6

The Pearl Index (PI) for women aged 18-35 years was estimated to be 0.38 for NOMAC/E2 (95% CI 0.10-0.97, n=1315) and 0.81 for DSRP/EE (95% CI 0.17-2.35, n=442). This calculation was based on pregnancies that occurred after the onset of treatment and within two days after the last pill intake.6 NOMAC/E2 demonstrated a high level of contraceptive efficacy and was shown to deliver withdrawal bleeds of shorter duration (3-4 vs. 5 bleeding/spotting days,6 p<0.0001[7]) and lighter intensity (2 vs. 3 bleeding days,6 p<0.0001[8]) when compared to DRSP/EE. A higher incidence of absent withdrawal bleeding occurred with NOMAC/E2 ranging from 22% (cycle 4) to 31% (cycle12) (p<0.05 vs. DRSP/EE for cycles 2-12).6 Twenty eight per cent (28%) of women missed one or more withdrawal bleeds in at least one of cycles 2, 3 or 4. Of these women, the incidence of absent withdrawal bleeding in cycles 5-13 ranged from 51% to 62%.1

The mean weight increase for subjects on NOMAC/E2 was 1kg over one year (p=0.001 vs. DRSP/EE; mean weight increase 0.35kg). Most women reported no impact on weight for both products (NOMAC/E2; 91.3% did not report weight gain or loss, 7.9% reported weight gain, 0.8% reported weight loss: DRSP/EE; 93.6% did not report weight gain or loss, 6.2% reported weight gain, 0.2% reported weight loss).[9]

Most women reported no impact on skin. There was no change in acne severity reported at last measurement for approximately 75% of women in both treatment groups both with or without acne at baseline.6 For NOMAC/E2 and DRSP/EE respectively improvement in acne was observed in 15.9% and 20.1% of women. Worsening or development of new acne was observed in 9.9% of women taking NOMAC/E2 and 4.0% of those randomised to DRSP/EE.6

Safety and tolerability of NOMAC/E2

51.2% of women receiving NOMAC/E2 and 37.0% of women randomised to DRSP/EE experienced adverse events (AEs) that were determined by the investigator to be treatment-related.6 The most frequently reported NOMAC/E2 treatment-related AEs (related incidence ≥ 5%) were acne (15.3% vs. 7.1% for DRSP/EE); irregular withdrawal bleeding (11.7% vs. 0.4% for DRSP/EE); increased weight (7.9% vs. 6.2% for DRSP/EE); and headache (6.6% vs. 6.2% for DRSP/EE).6

Serious AEs (SAEs) were reported for 2% of participants and were evenly distributed between the two treatment groups.6 Three SAEs were deemed as (possibly) treatment-related by the investigators, one in the NOMAC/ E2 group (severe menorrhagia) and two in the DRSP/EE group (deep vein thrombosis and systemic lupus erythematosus with concomitant patellar tendon bearing).6

The effect of NOMAC/E2 on parameters of haemostasis10,11 lipid metabolism, carbohydrate metabolism, sex hormone binding globulin and c-reactive protein11 have been studied in clinical trials but conclusions regarding the clinical relevance of the observed effects cannot be drawn.

Combined oral contraceptives

Combined oral contraceptives (COCs) contain an oestrogen component and a progestogen component. The type and amount of progestogen and oestrogen varies between different COCs. Although different types of progestogens have been developed, the oestrogen component in most COCs since their introduction in the 1960s is ethinylestradiol (known as EE).

For further information about NOMAC/E2 please refer to the Summary of Product Characteristics (SPC).

Source

[1] Zoely Summary of Product Characteristics. MSD. December 2012.

[2] Christin-Maitre, S. et al. Comparison of a 24-day and a 21-day pill regimen for the novel combined oral contraceptive, nomegestrol acetate and 17β-estradiol (NOMAC/E2): a double-blind, randomized study. Hum Reprod. 2011;26(6):1338-1347.

[3] Office for National Statistics. Contraception and Sexual Health 2008/2009 2009. Last accessed 05 December 2012.

[4] Trussell, J. Contraceptive failure in the United States. Contraception 83 (2011) 397-404.

[5] Westhoff , C. et al . Efficacy, safety, and tolerability of a monophasic oral contraceptive containing nomegestrol acetate and 17beta-estradiol: a randomized controlled trial. Obstet Gynecol. 2012;119:989-99.

[6] Mansour, D. et al. Efficacy and tolerability of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 β -oestradiol in a 24/4 regimen, in comparison to an oral contraceptive containing ethinylestradiol and drospirenone in a 21/7 regimen. The European Journal of Contraception and Reproductive Health Care. December 2011; 16: 430-443.

[7] Data on file March 2013. Available from MSD on request.

[8] Data on file March 2013. Available from MSD on request.

[9] Data on file March 2013. Available from MSD on request.

[10] Gaussem, P. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. Thrombosis and Haemostasis 2011; 105: 560-567.

[11] Ågren UM, Anttila M, M ä enp ä ä -Liukko K, et al. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17 β -oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Health Care 2011;16:444-57.

Source: MSD