Mithra completes recruitment of Covid-19 Phase II Study
Mithra, a company dedicated to Women’s Health announces that it has completed recruitment of the Coronesta Phase II, aiming to assess the protective role of Estetrol in Covid-19 infection. Estetrol is a naturally occurring estrogen produced by the human fetus during pregnancy.
Estrogen's protective effect
Since early in the Covid-19 pandemic, it has been recognized that men are almost twice as likely to progress to severe Covid-19 disease and die than women. This male predominance of deaths is consistent with that seen in other infectious diseases caused by human coronaviruses, such as Severe Acute Respiratory Syndrome (SARS).
Estrogens are known to modulate the immune system and there is increasing evidence that estrogens may be playing an important role in improving the outcomes of Covid-19 infection. Estrogen acts on a protein known as Angiotensin Converting Enzyme 2 (ACE2) and enables its expression to be reduced. This ACE2 protein specifically serves as a gateway for certain coronaviruses to enter human cells. Recent international studies, such as the one conducted at King's College London(1), also support a protective effect of an estrogen present at high levels in the body of women infected by Covid-19.
International Panel of Experts
Mithra brought together an international panel of experts(2) in endocrinology, women’s health, infectious disease, and intensive care medicine, to present and discuss the different types of estrogens and how they are currently being studied as treatment for Covid-19 and other viral diseases. This Panel confirmed the strong scientific basis for estrogens as potential treatment of COVID-19 and other respiratory viral diseases, pending results of randomized controlled clinical trials.
“We have not been able to develop many effective medications for Covid-19, and so we need something more effective,” said Prof. Jean-Louis Vincent, Professor of Intensive Care Medicine, Université Libre de Bruxelles, and Dept. of Intensive Care, Erasme University Hospital, Brussels, Belgium. “Estetrol seems to have the advantages of transdermal estradiol in an oral form and could be an interesting option for both male and female patients”.
“There’s very low risk to using estrogens and there’s really good evidence for the way they work as immune modulators,” said Dr. Louise Newson, General Practitioner and Menopause Specialist, Newson Health, Stratford-upon-Avon, UK. “If clinical trial data are supportive in Covid-19, we should considering starting estrogen therapy early, in men as well as women. Men would likely only need to be given estrogens for a short period of time for Covid-19.”
Coronesta Phase II design The international Phase II Coronesta study aims to explore the action of Estetrol on the immune, inflammatory and vascular response of patients infected with Covid-19 and to establish whether Estetrol could reduce the risk of progression to more severe disease. This clinical trial is expected to be the first prospective clinical trial of an estrogen to report results in Covid-19.
The Phase II Study(3) is a multicenter, randomized, double-blind, placebo controlled Phase 2 study evaluating the efficacy, safety and tolerability of Estetrol 15 mg tablet relative to placebo in 175 hospitalized patients (male/female) with moderate Covid-19 (i.e., not on high flow oxygen or mechanical ventilation). This Clinical Program includes centres in Belgium, Russia and Poland, with subjects receiving an active dose or placebo for a treatment period of 21 days. The primary objective of this Phase II clinical trial is to assess the ability of Estetrol to improve the percentage of patients who recover after 28 days compared to placebo.
Graham Dixon, CSO Mithra Women’s Health, commented: “ We are pleased to confirm the completion of patient recruitment and to have received a positive safety assessment from the independent board of experts on the DSMB, allowing us to continue our clinical trial without any modification. In the current context of the fight against Covid-19, all possible therapies against this virus and its variants are a priority. Estrogens, and especially Estetrol, could offer promising therapeutic potential to address respiratory diseases, in particular Covid-19. We are looking forward to get the top-line results during this summer.”
(1) Costeira et al, 2020, Estrogen and COVID-19 symptoms: associations in women from the COVID Symptom Study
(2) Expert Panel “Estrogens: Harnessing the power of nature against COVID-19 and emerging viral infections”, 28 May 2021. Summary available on Mithra’s Investor website (Section Presentation).
(3) More information about Coronesta Study available here