Drovelis, Lydisilka (EU), Estelle (US)Contraception
Drovelis, Lydisilka (EU), Estelle (US)
New molecular entity
Development and Regulatory status
Recommended for approval (Positive opinion)
Phase III Clinical Trials
Mar 21Recommended for EU approval by CHMP - the full indication is "Oral contraception. The decision to prescribe the medicine should take into consideration the individual woman’s current risk factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with the medicine compares with other combined hormonal contraceptives (CHCs)." .
Mar 20Filed in EU via centralised procedure .
Oct 19Estelle is licensed for commercialisation to Mayne Pharma in the US. Mithra plans to launch Estelle in H1 2021 in the US. Earlier, in Sep 2018, Mithra and Gedeon Richter entered into a licensing and supply to commercialise Estelle in Europe .
Mar 19Mithra announces intention to submit NDA to the US FDA and MAA to the EMA for pregnancy prevention by end of 2019 .
May 18Mithra announces that the two pivotal PIII E4 FREEDOM trials fulfilled regulatory requirements for a minimum total of 20,000 cycles, of which 50% were from North America .
A fifth generation combined oral contraceptive, composed of estetrol (a natural oestrogen) and drospirenone. In the presence of estradiol acts as an estrogen antagonist. It also favours estrogen receptor (ER)-α; other estrogens favour ER-β.
The last survey on contraceptive use was done by the Office for National Statistics (ONS) in 2008-9 and at that time showed 75% of women aged 16-49 years use some type of contraception, 25% of women use the combined oral contraceptive pill (COCP) and 25% of women rely on male condom use .
Trial or other data
Nov 18Mithra announces the PIII E4 FREEDOM (US/CA) trial met both primary and secondary endpoints of contraceptive efficacy, with a Pearl Index of 2.41 per 100 women (98% efficacy). The secondary endpoints achieved included bleeding profile, cycle control, quality of life and safety and tolerability. The study for drospirenone (3mg) and estetrol (15mg) was recommended by the US FDA given the high level of socio-cultural and physical variability amongst the target population for COCs in the US. Mithra also completed enrolment of 500 obese women aged 16-50 years in a population pharmacokinetic sub-study. The sub-study is to determine the impact, if any, of demographic characteristics such as BMI, race, smoking and fed/fasted state on the absorption, distribution and excretion of estetrol/drosperinone. Data from the sub-study showed that the estetrol/drosperinone was comparable to the safest second generation levonogestrel-based COC (Melleva) and also to fourth generation COC, Yaz .
Aug 18Mithra Pharmaceuticals releases safety and efficacy results from the PIII E4 FREEDOM (EU/Russia) trial. The trial met its primary endpoints. Results also demonstrated achieved secondary endpoints including outstanding bleeding profile, cycle control, quality of life, safety and tolerability .
Apr 18PIII E4 FREEDOM trial completes (NCT02817828). The trial included an endometrial safety sub-study, a part of the phase III programme in Europe/Russia and a regulatory requirement, in which endometrial biopsies were obtained from 101 patients at both the screening visit and the seventh study visit, with the paired biopsies analysed to evaluate the potential impact of drosperinone/estetrol on the endometrium after at least 10 cycles of drosperinone/estetrol .
Aug 16PIII E4 FREEDOM trial, to evaluate safety and efficacy of a combined oral contraceptive (COC) containing estetrol (15mg) and drospirenone (3mg) in healthy female volunteers starts (NCT02817841). The study will enrol 2,148 volunteers in the US and Canada .
Feb 16PIII E4 FREEDOM trial to evaluate the contraceptive efficacy and safety of a combined oral contraceptive containing estetrol (15mg) and drospirenone (3mg) in female patients at risk for pregnancy starts (NCT02817828). It will enrol 1,577 patients in Belgium, Czech Republic, Finland, Germany, Hungary, Russia, Poland and Sweden .