Publication date: 30/01/2019
Mithra (Euronext Brussels: MITRA), a company dedicated to Women’s Health, today announced that its Phase III Estelle® study conducted in the United States and Canada successfully met its primary efficacy endpoint. Efficacy is well in line with expectations, similar to a recently FDA approved combined hormonal contraceptive (Annovera™ PI 2.98 [95% Confidence Interval 2.13-4.06]) per 100 woman-years of use) and to Lo-Loestrin® (PI 2.92 [95% Confidence Interval 1.94-4.21]), one of the best-selling Combined Oral Contraceptives (COC) in the United States with USD 527.7 million sales in 2018 (15% yoy growth). Estelle® is Mithra’s COC candidate, composed of Estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.
The safety profile is supported by the unique Mode of Action of E4, which is a native estrogen with selective action in tissues. Two earlier Phase II studies conducted by Mithra confirmed E4 has a minimal impact on liver cells and metabolic pathways, including on the coagulation parameters resulting in an overall beneficial hemostatic profile. These coagulation parameters are effected more negatively by Ethinyl-Estradiol (EE), present in most oral contraceptives, making Estelle® a promising new contraceptive solution for women with a unique benefit/risk profile.
Mitchell Creinin, Director of Family Planning at the University of California, Davis commented: “I am excited about the introduction of a truly new estrogen into the field of hormonal contraception. This novel product has great potential based on Phase 2 data which shows less effects on liver metabolism, lipids, and the coagulation profile as compared to contraceptives using ethinyl estradiol. The overall efficacy, safety and excellent cycle control demonstrated in the Phase 3 studies confirms that Estelle® offers a truly innovative, next-generation oral contraceptive option.”
François Fornieri, CEO Mithra Women’s Health, commented: “We are very pleased with the outcome of the U.S. / Canadian top-line results, which complete the Phase 3 program and clearly demonstrate that Estelle® is a novel, ‘next generation’ oral contraceptive option for women. We are delighted to be one step closer to bringing Estelle® to the U.S. market ($5.53 billion). We believe it has the potential to support healthcare providers and women in their choice of a predictable and effective contraceptive respecting women’s wellbeing and lifestyle with the greatest sense of safety.”
The study assessed the efficacy, cycle control, general safety and acceptability of Estelle® in healthy women aged 16-50 years and involved subject participation for 12 months (13 cycles, 1 cycle = 28 days). Women with a Body Mass index (BMI) up to 35.0 kg/m² were included in the study. The primary endpoint was contraceptive efficacy measured by the number of on-treatment pregnancies per 100 women per 12 months of exposure among the women aged 16-35 years old at study entry. Results showed a Pearl Index (PI) of 2.41 (95% confidence interval 1.73-3.88) during 13,979 at risk cycles, in the absence of other contraceptive methods.
Amongst women aged 16-50 years old at study entry, results showed a PI of 2.30 (95% confidence interval 1.67-3.64) during 15,797 cycles, with in the absence of other contraceptive methods. The PI corresponds to a 98% efficacy rate over one year of use, in line with the efficacy goals of the study.
Cycle control and bleeding profile, which are essential to women’s adherance, showed an excellent regular bleeding pattern similar to patterns seen with oral contraceptives containing EE. Safety, acceptability and general well-being of the subjects (measured by two questionnaires) were also analyzed. Results from the MDQ (menstrual distress questionnaire) and QoL (quality of life) questionnaire showed that Estelle® is well tolerated by women, while their overall quality of life is maintained. There were no lipid and metabolic changes. These results reinforce the safety profile of Estelle®.
Mithra (Euronext: MITRA) is dedicated to providing innovation and choice in women's health, with a particular focus on fertility, contraception and menopause. Mithra's goal is to develop new and improved products that meet women's needs for better safety and convenience. Its two lead development candidates - a fifth generation oral contraceptive, Estelle®, and a next generation hormone therapy, Donesta® - are built on Mithra's unique native estrogen platform (E4). Mithra also develops and markets complex therapeutics and offers partners a complete spectrum of research, development and specialist manufacturing at its Mithra CDMO. Mithra was founded in 1999 as a spin-off from the University of Liège by Mr. François Fornieri and Prof. Dr. Jean-Michel Foidart. Mithra is headquartered in Liège, Belgium. Further information can be found at: www.mithra.com