Market Overview

Millendo Therapeutics Announces Publication of Positive Phase 2 Data for MLE4901 for the Treatment of Vasomotor Symptoms


Therapeutics, Inc.
, a clinical-stage biopharmaceutical company
focused on developing novel treatments for endocrine diseases caused by
hormone dysregulation, today announced the publication of positive data
from a Phase 2 investigator-initiated clinical trial of MLE4901,
previously known as AZD4901, for the treatment of menopausal vasomotor
symptoms (VMS), which are defined as hot flushes/flashes and night
sweats and affect 70% of menopausal women. The article, titled
"Neurokinin 3 receptor antagonism as a novel treatment for menopausal
hot flushes: a phase 2, randomized, double-blind, placebo-controlled
trial," was authored by the study investigators and published online in The
Lancet. The results of the study will also be presented today in
an oral presentation at the annual meeting of The Endocrine Society
(ENDO) in Orlando, Florida at 12:30pm EDT in room W414A of the Orange
County Convention and Exhibition Center.

As reported in the manuscript, the Phase 2 study met its primary
endpoint. Treatment with MLE4901 twice daily significantly reduced the
total weekly number of hot flushes during the final week of a 4-week
treatment period by 73% compared to a 28% reduction with placebo
(p<0.0001). Treatment with MLE4901 also significantly reduced weekly hot
flush severity, bother, and interference by 41%, 45%, and 58%,
respectively, compared to placebo (each p<0.0001). MLE4901 was well
tolerated, and no serious adverse events occurred. Three participants
developed a mild, reversible, asymptomatic transaminase rise with a
normal bilirubin after 28 days of treatment with MLE4901.

"The current standards of therapy for VMS, including hormone replacement
therapy (HRT), selective serotonin reuptake inhibitors (SSRIs), and
over-the-counter treatments, all have tradeoffs between safety and
efficacy such as an increased risk of breast and endometrial cancers,"
said Waljit S. Dhillo, Ph.D., Professor of Endocrinology and Metabolism
at Imperial College London and principal investigator of the study.
"While larger scale studies of longer duration will be needed, this
study has demonstrated the practice-changing capacity of MLE4901 for the
treatment of VMS in that it has the potential to treat hot flush
symptoms without the need for oestrogen exposure."

"The results of this study provide a strong rationale for the expanded
development of MLE4901 into patients with VMS, for which there is a
clear need for an effective non-hormonal treatment option," said Julia
C. Owens, Ph.D., President and Chief Executive Officer of Millendo. "In
addition to the continuation of our Phase 2b clinical program in
polycystic ovary syndrome (PCOS), we plan to initiate a Phase 2b
clinical trial of MLE4901 in patients with VMS later this year."

The Phase 2 trial ( identifier NCT02668185)
was a randomized, double-blind, placebo-controlled, single-center
crossover study evaluating the effectiveness of MLE4901 in 28 patients
with VMS. Patients received four weeks of twice-daily MLE4901 or placebo
followed by a two-week washout period, then four weeks of whichever
intervention they did not receive first followed by a two-week
monitoring period. The primary outcome measure was the total number of
hot flushes during the final week of both treatment periods. The study
was carried out at Imperial College London and the research was funded
by the Medical Research Council and the National Institute for Health
Research (NIHR).

About Vasomotor Symptoms
Vasomotor symptoms (VMS), defined
as hot flushes/flashes and night sweats, are experienced by a majority
of women during menopause. The sensations of heat and/or perspiration
associated with VMS occur randomly, generally last several minutes, and
are often preceded or followed by sensations of cold and/or shivering.
VMS tend to start in the peri-menopausal period and continue for an
average of 7.4 years, but may last for up to 15 years or more. VMS
interfere with the lives of affected women in a number of ways,
including disrupting the ability to sleep and concentrate and causing
anxiety and depression.

Up to 70% of women in menopause will develop VMS, with approximately 20
million women in the United States currently experiencing VMS. Current
standards of therapy for VMS include hormone replacement therapy (HRT),
selective serotonin reuptake inhibitors (SSRIs), and a variety of
over-the-counter treatments. None of these options has both a strong
safety and efficacy profile, and there is a clear need for an effective
non-hormonal treatment option.

About MLE4901
MLE4901 is an antagonist of the neurokinin 3
receptor (NK3R), which resides on the KNDy (kisspeptin/neurokinin
B/dynorphin) neuron. MLE4901 leverages recent biological insights that
elucidated the critical role of the KNDy neuron as a regulator of
reproductive hormonal signaling. MLE4901 is being developed for the
treatment of polycystic ovary syndrome (PCOS), one of the most common
hormonal endocrine disorders in women, and vasomotor symptoms (VMS),
defined as hot flashes and night sweats, which are experienced by a
majority of women during menopause.

About Millendo Therapeutics, Inc.
Millendo Therapeutics is
focused on developing novel treatments for endocrine diseases caused by
hormone dysregulation. Our mission is to build a leading endocrine
company that creates distinct and transformative treatments for a wide
range of diseases where there is a significant unmet medical need. We
are advancing two product candidates in five indications: MLE4901,
designed to address Polycystic Ovary Syndrome (PCOS) and Vasomotor
Symptoms (VMS), and ATR-101 for the treatment of Classic Congenital
Adrenal Hyperplasia (CAH), Endogenous Cushing's Syndrome (CS), and
Adrenocortical Carcinoma (ACC).

View Comments and Join the Discussion!

Partner Center