Elagolix has the potential to be an important treatment option
for long term medical treatment for Endometriosis, reports the results of two
replicate, randomized double blind, phase III studies. The paper was presented
at the 13th World Congress on Endometriosis in Vancouver, Canada and
simultaneously published in the New England Journal of Medicine.
Elagolix is
an oral gonadotropin-releasing hormone (GnRH) receptor antagonist. It results
in rapid, reversible, dose-dependent inhibition of luteinizing hormone (LH) and
follicle-stimulating hormone (FSH) secretion, leading to reduced ovarian
production of the sex hormones, oestradiol and progesterone, while on therapy.
Medical
management of Endometriosis requires treatment for extended period and
physicians currently have very limited options in this regard. Treatment with gonadotropin-releasing
hormone (GnRH) agonists, such as leuprolide acetate cannot be extended beyond 6
months because of osteoporosis and sever vasomotor symptoms.
These
two-trial recruited 1,689 premenopausal women between the ages of 18 and 49
years, who had endometriosis and suffered from moderate to severe pain and had
a z score of more than -1.5 for bone mineral density at the lumbar spine,
femoral neck, or total hip. The study participants were from 151 sites in the
United States and Canada from July 2012 through May 2014 and for Elaris EM-II
at 187 sites on five continents from November 2013 through July 2015.
Each woman
was randomly assigned to receive 150 mg of elagolix once daily (lower-dose
group), 200 mg of elagolix twice daily (higher-dose group), or placebo.
The results were
evaluated in terms of proportion of women who had clinical response for dysmenorrhea
and non-menstrual pain after 3 months of treatment. Other relevant clinical parameters
tested were dyspareunia, use of rescue NSAIDs and opioids, dyspareunia and
non-menstrual pain at 6 months of treatment.
In both the trials,
women showed statistically significant response in terms of dyspareunia and
non-menstrual pain at 3 months of treatment as compared to placebo. The response
was sustained at 6 months of treatment for these two parameters.
Women who
received the higher dose of elagolix (200 mg twice daily) had significantly
better results with respect to the use of rescue analgesic agents at 3 months
and 6 months, dyspareunia at 3 months, and rescue opioid use at 3 months than
did those receiving placebo.
Treatment
with Elagolix improved the quality of life based on the 30-item Endometriosis
Health Profile dimensions in both groups as compared to placebo.
Because of
its hypoestrogenic effect, more than 70% women in the trial reported adverse
effect including hot flushes and changes in bone mineral density and lipid
levels but the frequency differed significantly between the higher and lower
dose groups.
Professor
Hugh Taylor, lead author of the resulting paper said, “The idea that we now
have choices with regards to the extent of oestrogen suppression is attractive,
as it allows us to provide a more personalised and individualised therapy.”
“With
elagolix – unlike with Lupron (leuprolide acetate)– we can partially suppress
oestrogen, unlike the “all or nothing” current approach,” he further added.
Elagolix is
currently being investigated in uterine fibroids and endometriosis, and has
been studied in over 40 clinical trials totalling more than 3,000 women.
AbbVie, the makers of the drug, plans to submit a New Drug Application to the
US Food and Drug Administration (FDA) for endometriosis in 2017.
Full text of
the article in NEJM can be accessed here.
