Finally, an oral drug found effective in treatment of Uterine Fibroids following successful phase-3 trial

Relugolix successfully reduced heavy menstrual blood loss among Japanese women in a Multicenter, Randomized, Double-Blind, Parallel-Group, Phase 3 Study to Evaluate the Efficacy and Safety of Oral relugolix 40 mg as compared with injectable leuprolide  in the Treatment of Uterine Fibroids.

Relugolix is an oral, once-daily, small molecule GnRH receptor antagonist that has been evaluated in almost 1,600 study participants in Phase 1, Phase 2 and Phase 3 clinical trials. In these trials, it has shown to suppress estrogen and progesterone levels in women and testosterone levels in men. (It is also being evaluated in advanced prostate cancer via ongoing phase-3 HERO study).

The drug is being developed by Switzerland’s Myovant Sciences along with Japan’s Takeda. They said that these results will support the other ongoing global trials evaluating the drug in endometriosis and uterine fibroid patients.

"The positive results of decreased menstrual bleeding from Takeda's Phase 3 study of relugolix in Japanese women with uterine fibroids provides strong support for Myovant's ongoing Phase 3 studies with relugolix in North America, Europeand other regions," stated Lynn Seely, M.D., President and Chief Executive Officer of Myovant Sciences in a press release. 

"Uterine fibroids result in debilitating heavy menstrual bleeding and anemia in millions of women throughout the world, oftentimes requiring a hysterectomy to control the bleeding.  Myovant is working to develop relugolix, an oral, once-daily medication that can potentially provide women with an alternative option to major surgery for the treatment of uterine fibroids."

The study recruited 288 women with heavy menstrual bleeding associated with uterine fibroids. They were randomized to receive either relugolix 40 mg, administered orally once daily, or leuprolide acetate, an injectable GnRH agonist, administered by subcutaneous injection every four weeks, at a dose of 1.88 mg or 3.75 mg, for 24 weeks. 

The amount of blood loss was assessed by Pictorial Blood Loss Assessment Chart, or PBAC self-reported by patient themselves. At entry into study all patient had PBAC ≥ 120.

In the study, relugolix successfully demonstrated that it was as good as leuprolide acetate with 82.2% of patients achieving a score of less than 10 on the PBAC, compared with 83.1% of patients treated with leuprolide acetate (p = 0.0013).

The incidence of adverse effects was nearly similar and varied according to the drug. Another phase 3 trial with relugolix is currently ongoing in Japan with 70 patients who also complained of pain because of fibroids.

Two more trials (LIBERTY 1 and LIBERTY 2) are ongoing and were initiated by Myovant in January 2017.  These trials are looking at reducing heavy menstrual blood loss by relugolix alone followed by leuprolide  as monotherapy, relugolix combined with low dose leuprolide  or placebo for 24 weeks. 

These two trials are looking at reduction in blood loss by at least 50%, decrease in pain and size of fibroid and safety of the drug, as evident by bone -mineral density.

Myovant is solely responsible for obtaining Food and Drug Administration (FDA) approval for relugolix in the United States and the results of Takeda study will definitely reinforce its application. 

The drug is also currently tested by two phase-3 ongoing trials for relieving endometriosis associated pain, named as SPIRIT 1 and SPIRIT 2. These two trials are still recruiting patients and will run through 2020. The trials will evaluate relugolix with and without low-dose hormonal add-back therapy, to avoid the iatrogenic menopausal side effects.

Dienogest is well tolerated and alleviates endometriosis related pain

Dienogest is highly effective and well tolerated in relieving chronic, debilitating pelvic pain of endometriosis including menstrual pain and dysparunia says results of a 12-month single-center clinical trial published ahead of print in Journal of Obstetrics and Gynecology.  This is the first new medical treatment for endometriosis related pain since a decade.

Dienogest is a synthetic oral progestogen and has recently been introduced as a new medical treatment for endometriosis in more than a decade. It is highly selective for progesterone receptor and displays strong progestational effects and moderate antigonadotrophic effects, but no androgenic, glucocorticoid or mineralocorticoid activity.

It also can be taken orally and have a long half-life for once daily administration.

Endometriosis affects 5 - 10 per cent of women of reproductive age and impacts a woman's social, professional and personal life.

This is an observational, single center trial that enrolled 132 women with a surgically confirmed diagnosis of endometriosis for more than 2 years or a clinical diagnosis of disease with endometriosis-associated pelvic pain score of at least 40 mm on a 100-mm visual analog scale (VAS).

The women were on Dienogest 2 mg daily at the time of entering into study for no more than 30 days.

Women were routinely assessed for pelvic pain at 1 (V1), 3 (V2), and 12 (V3) months of follow up.

The women reported considerable relief in pelvic pain: from an 8.9 baseline VAS to 2.4 at end of 1month treatment [V1], 1.1 at 3 months treatment [V2], and 0.8 at 12 months treatment [V3]).

Significant relief was also observed in dyspareunia, from a baseline score of 6.7 to 2.8, 1.4 and 1.4 at the end of 1,3 and 12 months respectively.

Patients also were relieved of dyschezia, from a baseline score of 5.7 to 1.2, 0.5 and 0.5 respectively at the predefined interval.

Most frequently reported side effects were changes in menstrual bleeding patterns, breast tenderness, weight gain, loss of interest in sex and vaginal dryness. But, only 21 patients discontinued the treatment because of side effects.  

In other similar clinical trials, it fared well and was not found inferior to depot leuprorelin in reducing pelvic pain and was not significantly different from intranasal buserelin and depot triptorelin in improving combined symptoms/signs scores or revised American Fertility Society (rAFS) staging scores, respectively.

Therefore , the researchers concluded, that oral dienogest offers an effective, generally well tolerated therapeutic option for the long-term treatment of endometriosis.