FDA approval, global partnership on the agenda at Mithra as phase 3 menopause trials hit goals—with one blemish 

Mithra has brushed off a missed co-primary endpoint in one of its two phase 3 clinical trials and given a bullish update (PDF) on the menopause drug, which it expects to gain a global partner this year and go on to win approval on both sides of the Atlantic in 2024. Shares in the Belgian biotech rose 9% to around 22 euros ($25).  

The phase 3 program enrolled 2,300 postmenopausal women across two studies, one in North America and the other in Europe and Latin America. Participants in both studies were randomized to receive one of two doses of Donesta or placebo to test the effect of the oral estetrol-based hormone therapy on hot flushes.

Mithra hit all its co-primary endpoints in the European study but missed one of the four in the U.S. trial. The missed endpoint looked at the severity of vasomotor symptoms, the medical term for hot flushes, at Week 4. Mithra said the severity assessment reached statistical significance at Week 5. All the other three co-primary efficacy endpoints, which looked at severity at Week 12 and frequency at weeks 4 and 12, were met in both clinical trials. 

The miss against one of the co-primary endpoints is a blemish. But with the frequency and severity of hot flushes falling throughout the trials, to respectively end down 80% and 56% from baseline at Week 12, Mithra thinks it has the efficacy data to support filings for approval.

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“We believe that we are in a strong position to convince agencies that these efficacy results support approval of Donesta. The p-value observed at week four for the severity [in the U.S. trial] is borderline to statistical significance. And then if we look at the global data package, we reach statistical significance on all co-primary endpoints. So, we believe internally, with our medical and regulatory teams, that this will be able to be approved,” Graham Dixon, Ph.D., Mithra’s chief scientific officer, said in a conference call. 

Mithra, which said it has “very positive” quality-of-life data from the European clinical trial, expects to have three- and 12-month secondary endpoint results from the U.S. study by the end of the year. Work to gather the secondary endpoint data is progressing alongside the collection of safety data. With safety data from the two studies due at the end of 2022 and first half of 2023, Mithra thinks it is on track to win approval in the U.S. and Europe in 2024. 

The safety readout could be important for the commercial chances of Donesta. Mithra’s market research found half of women don’t seek medical treatment for menopause because of safety concerns. f which has a different mode of action, may have a better side effect profile. Specifically, Mithra expects its candidate to have less of an impact on the liver and the breast than other estrogens.

Mithra is now working to secure a global partner for the asset. “We still expect to sign an agreement in 2022,” Jean-Manuel Fontaine, chief business officer at Mithra, said. “Obviously, the data that's been released today is going to be supportive of the discussions. We have not been waiting, and the partners have not been waiting, for the full dataset to enter into an agreement.”