16 October 2017
MITHRA ANNOUNCES COMPLETION OF RECRUITMENT IN DONESTA® PHASE II STUDY
Donesta® Phase II study remains on track to report top line data late Q1 2018
260 women recruited in total, of which 86 have already completed at least 12 weeks of treatment as part of the Phase II study
Liège, Belgium, 13 October 2017 – Mithra (Euronext Brussels: MITRA), a company specialized in Women’s Health, today announces the completion of recruitment in the E4 Relief Phase II study of Donesta®, Mithra’s next-generation hormone therapy (HT) candidate with oral administration of Estetrol (E4) for Vasomotor Menopausal Symptoms (VMS) relief. Top-line data, based on 12-weeks of treatment, remain on track to be reported late in the first quarter of 2018.
The E4 Relief dose-finding study includes centres in the Czech Republic, Poland, Belgium, the Netherlands, Ireland and the UK, with subjects receiving Donesta® for a treatment period of 12 weeks. The primary objective of the Phase II clinical trial is to identify the oral daily minimum dose of Donesta® required to effectively treat VMS, or hot flushes, in post-menopausal women. In total four dose levels of Donesta® are being tested compared to placebo in this double-blinded study. Secondary outcomes include an evaluation of other menopausal symptoms such as vulvo-vaginal atrophy (VVA), or vaginal dryness, lipid and glucose metabolism as well as bone metabolism markers. The study will also analyze key safety issues including endometrial thickness.
Research shows that current HT-based treatments may increase the risk of breast cancer and venous thromboembolic events (VTE) such as blood clots,. Thanks to the unique mode of action of the native estrogen E4, Donesta® has the potential to offer an improved safety profile, addressing the unmet medical need in menopause,,.
The global menopause market currently stands at USD 8.6 billion and is expected to grow to approximately USD 16 billion by 2025, driven by growing awareness for Women’s Health issues, the unmet medical need in menopause, and the aging population, in addition to market expansion with the availability of new treatment options that provide a safer alternative to currently available therapies.
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 Baber RJ, et al. 2016 IMS Recommendations on women's midlife health and menopause hormone therapy. Climacteric 2016; 19:109–150.
 Coelingh Bennink H, et al. Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study. Menopause 2017 (Vol. 24:6)
 Gerard C, et al. Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms. Oncotarget 2015; 6:17621–17636.
 Abot A, et al. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor modulation, uncoupling nuclear and membrane activation. EMBO Molecular Medicine 2014 6 1328–1346.
 Transparency Market Research 2017
“Today’s news is an important milestone in the development of Donesta®. The study is on track to report top line results in Q1 2018, and the results may corroborate earlier studies indicating E4’s unique potential to address menopausal symtoms with an improved safety profile versus current estrogen-based HT products. We are encouraged by the number of women that have already completed the full 12 weeks of treatment, providing an indication of the user acceptance of Donesta®. If approved, Donesta® could represent an important novel and differentiated therapy in the very large, and rapidly growing, menopause market.”
François FornieriCEO of Mithra
About the E4 Relief Donesta® Phase II study
Donesta® is a next generation orally administered hormone therapy based on E4 for vasomotor menopausal symptoms (VMS). In May 2016, Donesta® entered into a European Phase II dose-ranging study, E4 Relief (MIT-Do0001-C201) in 260 women aged 45-65 in the Czech Republic, Poland, Belgium, the Netherlands, Ireland and the UK, for a treatment period of 12 weeks. Four doses of Donesta® (2.5 mg, 5 mg, 10 mg and 15 mg) compared to placebo are being tested to establish the minimum effective dose. For non-hysterectomized women, E4 therapy is followed by a progestin therapy (Dydrogesterone 10 mg) for 2 weeks as a protective measure to curb any endometrial growth.
The primary endpoint is an evaluation of the changes in frequency and severity of moderate to severe VMS (vasomotor sypmtoms or hot flushes). Secondary outcomes include: (1) evaluation of the effects of different doses on vulvovaginal atrophy, on vaginal maturation index and on vaginal pH; (2) evaluation of additional secondary endpoints, including bone parameters, lipid & glucose metabolism, hemostatic laboratory variables, PK and women satisfaction; (3) a safety assessment, with most importantly a measurement by transvaginal ultrasonography of the change in endometrial thickness at each study visit.
Mithra has contracted Synteract HCR as CRO for the E4 Relief study.
For more information, please contact:
Sofie Van Gijsel, IRO
+32 485 19 14 15
Consilium Strategic Communication
Jonathan Birt, Sue Stuart, Philippa Gardner, Ivar Milligan, Hendrik Thys
+44 2 037 095 700
Chief Communication Officer
+32 4 349 28 22 / +32 475 86 41 75
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 next-generation hormone therapy Donesta® - are built on Mithra’s unique natural estrogen platform, E4 (Estetrol). Mithra also develops, manufactures and markets complex therapeutics and offers partners a complete spectrum of research, development and specialist manufacturing at its 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
The contents of this announcement include statements that are, or may be deemed to be, "forward-looking statements". These forward-looking statements can be identified by the use of forward-looking terminology, including the words "believes", "estimates," "anticipates", "expects", "intends", "may", "will", "plans", "continue", "ongoing", "potential", "predict", "project", "target", "seek" or "should", and include statements the Company makes concerning the intended results of its strategy. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. The Company's actual results may differ materially from those predicted by the forward-looking statements. The Company undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law.
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