Mithra announces positive top-line results from Donesta® Phase 3 studies in menopausal women

Launched in late 2019, the Phase 3 Clinical Program carried out in 2,300 postmenopausal women (40- 65 years) includes 2 pivotal studies: one in North America (C302); and a second in 14 countries in Europe, Latam and Russia (C301). Both studies are worldwide randomized, multicentre, double-blind, placebo-controlled trials. This Phase 3 Program aims to measure the treatment effects of vasomotor symptoms’ frequency and severity at 15mg and 20 mg doses of E4, especially for hot flushes. The coprimary efficacy endpoints are the mean change from baseline in the frequency and severity of moderate to severe VMS at week 4 and week 12 compared to placebo.

Both studies demonstrated a meaningful reduction in VMS frequency and severity from baseline and compared to placebo. At week 12, the results showed a reduction up to 80% in the frequency of hot flushes when compared to baseline. Regarding the severity, this reduction was up to 56% compared to baseline. All co-primary efficacy endpoints were statistically (all p<0.01) met in both studies, except for a borderline non-significant result for the severity criteria at week 4 in the C302 study, which reached and exceeded statistical significance by week 5 (p<0.01). Both studies also showed that the number and severity of hot flushes continued to decrease week after week until the end of the study, i. e. 3 months of treatment. Secondary endpoints evaluated at 3 months in the C301 study suggest a very positive impact of Donesta® on the quality of life (hot flushes, mood swings, anxiety, sleep, joint pain, skin & hair quality, libido,…) as measured by validated patient-reported outcome questionnaire. For C302 study, results for secondary endpoints at 3 and 12 months are expected end 2022.

Graham Dixon, CSO Mithra Women’s Health, commented: “These positive top-line results demonstrate that Donesta® reduces significantly the frequency and severity of hot flushes and therefore strongly improves the daily quality of life of menopausal women. Menopause lasts for an average of 7 years and requires a safe long-term treatment that can act both on the main symptoms strongly impacting women's private and professional lives, and offer an advantageous benefit/risk profile. These first Phase 3 positive data allow us to pursue with confidence our clinical and regulatory activities. We look forward to receiving the safety data by the end of this year, as well as additional data on all secondary endpoints related to quality of life. Today, we are even more convinced that Donesta® can be a game-changer, offering a global solution to address the unmet needs of menopausal women.”

Clinical Program moving forward

The Donesta® Phase III Clinical Program is still ongoing with patients completing a treatment duration for 52 weeks. Regarding the safety, the independent Data and Safety Monitoring Board (DSMB) completed its last 2021 safety assessment of the Phase 3 Clinical Program of Donesta®. Experts confirmed an expected pharmacological profile during the trial from initiation until the safety evaluation of 2213 subjects treated and recommended to carry on the studies without modification. The primary safety data are anticipated at the end 2022 for the American study and for end H1 2023 for the European study. Depending on the evolution of the Covid-19 situation, study results and regulatory authorizations, Mithra believes it could achieve marketing authorization for Donesta® in H1 2024 for the United States and in H2 2024 for Europe. Convinced of the potential of Donesta® on other major estrogen deficiency symptoms, Mithra also decided late 2021 to broaden the scope of its Clinical Program with three additional studies on the effect of E4 on vulvovaginal atrophy, skin and hair quality. These studies will be launched in 2022, depending on regulatory agency feedback. As presented during Mithra’s Investor Day held in November 2021 (1), a quantitative market research program surveying over 1000 prescribers and women confirmed a large unmet medical need in the menopause market. One in two women currently do not seek medical treatment because of their safety concerns of current hormonal treatment. The research confirmed that women suffer from bothersome symptoms beyond VMS and highlighted the significant opportunity for a novel, safe hormone therapy to treat menopausal symptoms beyond VMS. The global menopause market is currently worth nearly USD 10 billion and is expected to reach around USD 17 billion by 2027 (2).

Leon Van Rompay, CEO Mithra Women’s Health, commented: “2021 was an incredible year marked by the worldwide launch of our first estetrol product and 2022 is starting off in another great way with these positive efficacy results, which confirm the strong potential of Donesta® as an innovative hormone therapy targeting several major menopausal symptoms. We clearly believe that the unique profile of Donesta® could provide relief for millions of menopausal women in their daily struggle against the negative effects of estrogen loss during menopause.”

(1) Investor Day webcast 29/11/2021

(2) Market Research Future, 2020; IQVIA 2019