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.