Pantarhei Oncology (PRO), a subsidiary company of Pantarhei Bioscience, is developing estetrol (E4) for oncological and veterinary E4 applications, including breast cancer and prostate cancer. For both indications, proof-of-concept has been achieved successfully. Phase II clinical studies have demonstrated promising anti-tumor activity and major improvement of quality of life in patients with advanced hormone sensitive breast and prostate cancer (dual efficacy). Advisory boards with well-respected international experts have been installed for the indications breast cancer and prostate cancer. Based on a positive outcome of the FDA Pre-IND meeting, the project is ready for Phase III development for the prostate cancer indication.
Pantarhei is potentially interested in (pharmaceutical) partners for the further oncological development of E4. The breast cancer project is ready for Phase IIB and prostate cancer for Phase III development. The breast cancer and prostate cancer indications are patent protected until 2037 respectively 2038.
Estetrol (E4) is an estrogen, produced by the human fetal liver during pregnancy. It is present in high concentrations in the blood of pregnant women and at even higher levels (10-20 times) in fetal blood at parturition. This high exposure of the vulnerable developing fetus implies that E4 might be a safe estrogenic steroid for human use. Estetrol was identified by Egon Diczfalusy at the Karolinska Institute in Stockholm (Sweden) in 1965. It has been discovered as a potential new drug for human use by Herjan Coelingh Bennink at Pantarhei Bioscience (PRB) in 2000.
From 2001-2015 PRB has performed pre-clinical and clinical Phase I/II development of E4 for Women’s Health applications such as contraception and menopausal hormone therapy and Reproductive Endocrine Oncology (REO). The most important (pre-)clinical studies have been reported in a special Supplement of the journal Climacteric in 2008 and other peer-reviewed journals. It was found that E4 behaves pre-clinically and clinically as an estrogen, however remarkably with estrogen-antagonistic effects in breast cancer models.
Between 2009 and 2013 PRB developed E4 in a Phase II program for oral contraception in the joint venture Estetra SA with the Belgian company Mithra Pharmaceuticals. Those studies in more than 400 women showed that E4 is effective and safe in a dose of 15-20 mg per day, in combination with a progestin.
In 2015 Pantarhei sold all rights, assets and patents of E4 to Mithra Pharmaceuticals. All rights for oncological and veterinary E4 applications (including breast cancer and prostate cancer) were exclusively licensed back to PRB and product development was continued by Pantarhei Oncology.
Mithra is developing the women’s health applications of E4 (i.e. hormonal contraception [Estelle®] and menopausal hormone therapy [Donesta®]). In 2020, Mithra has successfully filed Estelle® in Europe (EMA), in the US (FDA) and in other regions. The EMA has recognised E4 as a New Active Substance in November 2020. In March 2021, the Canadian authorities “Health Canada” were the first in the world to approve Estelle® as a new combined oral contraceptive medicine. This was followed by an approval of the Food & Drug Administration (FDA) in April 2021 and an approval of the European Commission in May 2021. Launch of the new combined oral contraceptive containing 15 mg E4 and 3 mg drospirenone in Canada, US and Europe took place in the second half year of 2021. For the indication menopausal hormone therapy, Phase III clinical studies are currently ongoing. The first positive top-line results from Donesta® Phase III studies were announced by Mithra in January 2022.