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A new class
of drug Neurokinin 3 (NK3) receptor antagonists is highly effective and low
risk alternative to hormone replacement therapy(HRT) for treatment of
menopausal hot flashes according to a study presented at the ENDO 2017, The
endocrine society annual meeting from April 1–4, 2017, in Orlando, FL.
The study results
of MLE4901 trial were also simultaneously published in Lancet.
About two-third
of women are affected by hot flashes that reduce the quality of life and
overall well-being. Approximately 20 million women in the United States
currently experiencing VMS. HRT is effective alternative, but it is not without
any side effects and cannot be used in patients with malignancies.
In this
phase2, randomized, double-blind, placebo-controlled, single-center, crossover trial
37 women aged 40–62 years were assigned to take either 40 mg BD of the drug/placebo
for 4 weeks and then received other treatment for 4 weeks after a 2 weeks’ gap
in between.
The primary
end point of study was number of hot flashes, the secondary endpoints were hot
flush severity, bother, and interference with daily activities, gonadotrophins
and LH concentrations.
MLE4901
reduced the number and severity of hot flashes considerably as compared to placebo
(p<0·0001 for both).
The women
also reported increased sleep, decreased fatigue and irritability. The drug was
well tolerated except a small increase in transaminase without rise in serum
bilirubin.
Studies
during the last 2 decades have increasingly shown the role of NKB–NK3R signaling
in the etiology of menopausal hot flushes.
Dr Julia K
Prague, of Imperial College London, United Kingdom, said of MLE4901 in her
presentation"Treatment with the NK3 receptor antagonist could be
practice-changing, as it significantly relieves hot-flash symptoms without the
need for estrogen exposure. Larger-scale studies of longer duration are now
indicated and planned."
The other
study presented at the conference evaluated the effect of fezolinetant, which was a 12-week double-blind, placebo-controlled, multicenter study
involving 80, healthy postmenopausal women between 40-65 years.
The women
were randomized to receive either fezolinetant (90 mg, BID) or placebo. Women
receiving the NK3 antagonist experienced 50% less frequent hot flashes that
were half as severe as women in the placebo group. (P < .001)
At a biochemical
level these women showed a 50% decrease in LH levels. LH levels are biomarkers
for reduction in hot flashes. Quality of life, sleep and irritability also improved,
that continued after stopping the drug.
Both the
drugs did not have any significant effect on libido, "That is to be
expected, because after all this isn't estrogen replacement," said the
lead author Dr Fraser. He further added
that the safety profile is extremely good and only two patients experienced mild
side effects and the patients were able to reach the end of study.
Ogeda chief
scientific officer Dr Graeme L Fraser, who presented the fezolinetant data,
said that the company plans to further test the drug in women who have had breast,
uterine, and ovarian cancer, for whom hormone-replacement therapy is
contraindicated. "This really is a perfect fit for this population, where
there is an important unmet need."
Pr. Herman
Depypere (UZ Ghent), principal investigator said: "More than 80% of
menopausal women develop hot flashes and 20% to 30% of this population seek
treatment because their symptoms are severe and debilitating and negatively
affect their quality-of-life. The Women's Health Initiative Study advises
against the chronic use of HRT due to important safety concerns including the
increased risks of cancer and cardiovascular events. The degree of relief
demonstrated with fezolinetant (a non-HRT) in this study could represent an
important breakthrough in the way we can manage menopause."
The results
of both these studies call for larger studies for long period of time.
