Zoely (nomegestrol/estradiol) / Merck (MSD) - LARVOL DELTA

Petroclival meningioma regression after combined oestrogen and nomegestrol acetate interruption. (PubMed, BMJ Case Rep) - "After cessation of Zoely, the patient showed clinical improvement and shrinkage of the tumour volume from 27.22 cm3 to 20.54 cm3 in 6 months. This is probably the first report of spontaneous meningioma regression after Zoely interruption."

Journal • Brain Cancer • CNS Tumor • Meningioma • Oncology • Solid Tumor

A Dose-Finding Study to Evaluate Ovarian Function and Vaginal Bleeding in Next Generation Rings (P06109/MK-8175A/MK-8342B-012) (clinicaltrials.gov) - P2 | N=666 | Completed | Sponsor: Organon and Co | Phase classification: P2b ➔ P2

Phase classification

Zoely vs. Zoloft in Premenstrual Dysphoric Disorder (ANZCTR) - P2 | N=160 | Recruiting | Sponsor: Monash University | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression

Contraceptive Efficacy and Safety of NOMAC-E2 Combined Oral Contraceptive (clinicaltrials.gov) - P3 | N=2007 | Terminated | Sponsor: Organon and Co | This decision was made for business reasons unrelated to safety. None of the pre-specified efficacy endpoints were analyzed.

Trial completion date • Trial primary completion date • Trial termination

A review of the pharmacology, clinical outcomes, and real-world effectiveness, safety, and non-contraceptive effects of NOMAC/E2. (PubMed, Eur J Obstet Gynecol Reprod Biol X) - "Nomegestrol acetate + 17β-estradiol (NOMAC/E2) is a combined oral contraceptive (COC) that inhibits ovulation by suppressing ovarian function by a 17-hydroxy-progesterone derivative and an estrogen identical to that endogenously produced by the ovaries...Importantly, NOMAC/E2 is not associated with increased risk of venous thromboembolism, a major safety concern of healthcare professionals for women receiving hormonal contraceptives. This review highlights NOMAC/E2 as a differentiated option among COCs and could help inform oral contraceptive choice to ultimately improve patient management and outcomes in real-world settings."

Clinical data • Journal • Real-world • Real-world effectiveness • Real-world evidence • Review • Acne Vulgaris • Cardiovascular • CNS Disorders • Depression • Endometriosis • Gynecology • Hematological Disorders • Metabolic Disorders • Venous Thromboembolism • Women's Health

Contraceptive Efficacy and Safety of NOMAC-E2 Combined Oral Contraceptive (clinicaltrials.gov) - P3 | N=1878 | Active, not recruiting | Sponsor: Organon and Co | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2024 ➔ Oct 2024 | Trial primary completion date: Mar 2024 ➔ Oct 2024

Enrollment closed • Trial completion date • Trial primary completion date

Is the multinational, surveillance PRO-E2 study informative for all countries? The Italian data on VTE and contraceptive effectiveness. (PubMed, Eur J Contracept Reprod Health Care) - "This subgroup analysis of the PRO-E2 study provides comprehensive epidemiological data on the use of combined oral contraceptives in a large Italian cohort, with a higher prevalence of women over 35 years and smokers. The study confirms the low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 pill."

Journal • Cardiovascular • Hematological Disorders • Pulmonary Embolism • Respiratory Diseases • Venous Thromboembolism

Zoely vs. Zoloft in Premenstrual Dysphoric Disorder (ANZCTR) - P2 | N=160 | Not yet recruiting | Sponsor: Monash University | N=240 ➔ 160

Enrollment change • CNS Disorders • Depression

Zoely vs. Zoloft in Premenstrual Dysphoric Disorder (ANZCTR) - P2 | N=240 | Not yet recruiting | Sponsor: Monash University

New P2 trial • CNS Disorders • Depression

NOMAC-E2 compares to LNG combined oral contraceptives in women over forty: real-world PRO-E2 study. (PubMed, Gynecol Endocrinol) - "No differential effect on mood and weight was observed between cohorts. NOMAC-E2 can be considered a valid alternative to COC in perimenopausal women."

Journal • Real-world • Real-world evidence • Cardiovascular • Venous Thromboembolism

NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives in women under 25: real-world PRO-E2 study. (PubMed, Gynecol Endocrinol) - "The HR for unintended pregnancy comparing NOMAC-E2 to COC was 0.47 (95% CI, 0.31-0.71) and the HR was 0.52 (95% CI, 0.34-0.78). No differential effect on acne, mood, and weight was observed between cohorts. NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COC."

Journal • Real-world • Real-world evidence • Acne Vulgaris

NOMAC-E2 compares to LNG combined oral contraceptives in women over forty: real-world PRO-E2 study (ESCRH 2022) - "Although the overall number of events was low, the presented data indicates no substantial differences between women using NOMAC-E2 or COCLNG in VTE risk, contraceptive effectiveness and symptom management in women transitioning to menopause. Thus, NOMAC-E2 can be considered a valid alternative to the gold standard in this population. [1] First-ever users of an eligible COC or restarting with an eligible COC (same COC as before or a new COC) after a break of at least 2 months."

Clinical • Real-world evidence • Cardiovascular • Hematological Disorders • Respiratory Diseases • Venous Thromboembolism

SPOSY 05 Sponsored Symposium Theramex; A large multinational Real-world study confirms efficacy and tolerability of Zoely (NOMAC/E2) (ESCRH 2022) - "Sponsored by Theramex"

Clinical • Real-world evidence

NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives and has no adverse effect on mood, acne or weight change in women under 25: real-world PRO-E2 study (ESCRH 2022) - "NOMAC-E2 shows a favourable profile in young women, with a significantly better contraceptive effectiveness than the gold-standard COCLNG and without an association with negative changes in mood, acne and weight over time. [1] First-ever users of an eligible COC or restarting with an eligible COC (same COC as before or a new COC) after a break of at least 2 months."

Adverse events • Clinical • Real-world evidence • Acne Vulgaris • Cardiovascular • Hematological Disorders • Respiratory Diseases • Venous Thromboembolism

NOMAC-E2 compares to LNG combined oral contraceptives in women over forty: real-world PRO-E2 study (ISGE 2022) - "Thus NOMAC-E2 can be considered a valid alternative to the gold standard in this population. *First-ever users of an eligible COC or restarting with an eligible COC (same COC as before or a new COC) after a break of at least 2 months."

Clinical • Real-world evidence • Cardiovascular • Hematological Disorders • Respiratory Diseases • Venous Thromboembolism

NOMAC/E2 in perimenopausal women – evidence from PRO-E2 (ISGE 2022) - No abstract available

Clinical

NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives and has no adverse effect on mood, acne or weight change in women under 25: real-world PRO-E2 study (ISGE 2022) - "Conclusions NOMAC-E2 shows a favourable profile in young women, with a significantly better contraceptive effectiveness than the gold-standard COCLNG and without an association with negative changes in mood, acne and weight over time. *First-ever users of an eligible COC or restarting with an eligible COC (same COC as before or a new COC) after a break of at least 2 months."

Adverse events • Clinical • Real-world evidence • Acne Vulgaris • Cardiovascular • Hematological Disorders • Respiratory Diseases • Venous Thromboembolism

Contraceptive Efficacy and Safety of NOMAC-E2 Combined Oral Contraceptive (clinicaltrials.gov) - P3 | N=1878 | Recruiting | Sponsor: Organon and Co

New P3 trial

Unintended pregnancy in users of nomegestrol acetate and 17β-oestradiol (NOMAC-E2) compared with levonorgestrel-containing combined oral contraceptives: final results from the PRO-E2 study. (PubMed, Eur J Contracept Reprod Health Care) - "The HR of NOMAC-E2 vs COC was 0.45 (95% CI, 0.34-0.60; adjusted for age, body mass index, gravidity, COC user status, education level). NOMAC-E2 demonstrated superior contraceptive effectiveness compared to COC, likely due to the comparatively short hormone-free interval and possibly reinforced by the long half-life of NOMAC."

Clinical • Journal

Prospective controlled cohort study on the safety of a monophasic oral contraceptive containing nomegestrol acetate (2.5mg) and 17β-oestradiol (1.5mg) (PRO-E2 study): risk of venous and arterial thromboembolism. (PubMed, Eur J Contracept Reprod Health Care) - "The risk of all VTE and ATE was not higher in NOMAC-E2 users compared with COCLNG users. NOMAC-E2 use was not associated with a higher risk of VTE or ATE compared with COCLNG."

Clinical • Journal • Cardiovascular • Hematological Disorders • Respiratory Diseases • Venous Thromboembolism

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study. (PubMed, Mult Scler) - "No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) (p = 0.79)). POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses."

Journal • CNS Disorders • Multiple Sclerosis

The effectiveness of quick starting oral contraception containing nomegestrol acetate and 17-β estradiol on ovulation inhibition: A randomized controlled trial. (PubMed, Sci Rep) - "Quick starting COC during day7-9 of menstrual cycle can inhibit ovulation for more than 90%. The quick starting NOMAC/E2 is non-inferior to GS/EE for preventing ovulation and suppressing follicular growth."

Clinical • Journal • Long-acting Reversible Contraceptives

A phase 2b multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of vaginal rings containing nomegestrol acetate or etonogestrel and 17β-estradiol in the treatment of women with primary dysmenorrhea. (PubMed, Contraception) - P2 | "This placebo-controlled study provides evidence that vaginal contraceptive rings containing NOMAC-E2 or ENG-E2 improve moderate to severe dysmenorrhea, across all of doses studied. This adds to the evidence that hormonal contraceptives are effective treatments for dysmenorrhea."

Clinical • Journal • P2b data

Nomegestrol acetate/17beta-estradiol does not negatively alter the vascular resistance of clitoral arteries: a prospective, exploratory study. (PubMed, Int J Impot Res) - "In the NOMAC/E2 group, at follow-up, uterine artery PI and acceleration were significantly reduced (p = 0.04), whereas no significant differences were observed in the HCs group; however, the change in uterine artery parameters did not differ significantly between the two groups. NOMAC/E2, differently from other COCs, does not negatively alter the vascular resistance of clitoral arteries and appears as a good contraceptive choice to protect both cardiovascular and sexual health."

Clinical • Journal