Myovant Sciences, a clinical-stage biopharmaceutical company, has announced the presentation of data from a placebo-controlled phase 2 dose-finding study conducted by Takeda Pharmaceutical Company Ltd. in Japan evaluating the ability of relugolix to decrease heavy menstrual bleeding in women with uterine fibroids. The study met its primary endpoint with relugolix demonstrating a marked decrease in menstrual blood loss from Week 6 to Week 12 as assessed by a patient-reported outcome (p < 0.0003 at relugolix 40-mg dose vs. placebo). The findings were presented during a poster session (Abstract #17H) on May 7 at the 2017 Annual Clinical and Scientific Meeting of the American Congress of Obstetricians and Gynecologists, which is being held in San Diego, California, May 6-9, 2017.
Relugolix demonstrated statistical significance over placebo in the primary endpoint of the proportion of subjects who had reduction in menstrual blood loss from a score of at least 120 required at study entry to less than 10 from Week 6 through Week 12 on the Pictorial Blood Loss Assessment Chart (PBAC). Relugolix decreased menstrual blood loss in a dose-dependent manner with the highest proportion of responses [84%, 95% confidence interval (74% to 93%) vs. placebo] in the relugolix 40-mg group.
In the relugolix 40-mg group, 73% of women achieved amenorrhea (i.e. a PBAC score of 0, representing no menstrual blood loss) from Week 6 through Week 12. No women in the placebo group achieved amenorrhea. At Week 12, the 40-mg group demonstrated an absolute reduction in myoma and uterine volumes of approximately 50% from baseline compared to placebo. By Week 12, there was an increase in hemoglobin levels in the relugolix 20- and 40-mg groups compared to placebo. Patient-reported pain from uterine fibroids, based upon the numerical rating scale (NRS) score, indicated that patients who received relugolix treatment had fewer pain symptoms from Week 6 to Week 12, with the relugolix 40-mg dose having the greatest reported reduction of pain symptoms.
The most commonly observed adverse events (occurring more than 10% more frequently in treatment groups vs. placebo) were mild or moderate in severity and included headache, metrorrhagia, menorrhagia, and hot flush. Bone mineral density decreased in a dose-dependent fashion with the greatest loss (-2.3%) observed in the relugolix 40-mg group.
"These data provide a strong basis for our ongoing phase 3 studies, LIBERTY 1 & 2, which are evaluating relugolix co-administered with low-dose hormonal add-back therapy in women with uterine fibroids and heavy menstrual bleeding," said Lynn Seely, MD, president & chief executive officer of Myovant Sciences. "Myovant hopes to provide women with a well-tolerated medical therapy to treat symptoms of uterine fibroids as an alternative to hysterectomy and other invasive procedures commonly performed to treat this condition."
The phase 2 multicenter, randomized, double-blind, parallel-group, placebo-controlled study conducted by Takeda Pharmaceutical Company was designed to evaluate the safety and efficacy of relugolix administered orally at a dose of 10, 20, or 40 mg once daily for 12 weeks in premenopausal Japanese women, 20 years of age or older, with a diagnosis of uterine fibroids confirmed by imaging or laparoscopy and heavy menstrual bleeding attributed to uterine fibroids (N = 216). Heavy menstrual bleeding was defined as a score on the PBAC of at least 120, which corresponds to a blood loss of approximately 80 mL.
The study consisted of a 4- to 12-week pretreatment period with a placebo run-in period that was initiated during the first menstrual cycle; after completion of the pretreatment period patients were randomly assigned to either a relugolix treatment group or placebo for a 12-week treatment period and a 4-week follow-up period. The primary outcome measure was the proportion of patients with a total PBAC score of less than 10 from Week 6 to Week 12. Secondary endpoints included the proportion of patients with amenorrhea (PBAC score of 0), changes in myoma and uterine volumes, change in hemoglobin, pain symptoms assessed by the NRS score, and quality of life symptom severity score assessed by the UFS-QOL score.
Relugolix is an oral, once-daily, small molecule that acts as a gonadotropin-releasing hormone (GnRH) receptor antagonist and has been evaluated in over 1,300 study participants in Phase 1 and multiple large controlled Phase 2 clinical trials. In these trials, relugolix has been shown to be generally well tolerated and to suppress estrogen and progesterone levels in women and testosterone levels in men. Common side effects are consistent with the lowering of estrogen and progesterone in women and testosterone in men.
Myovant Sciences has an exclusive, worldwide license (excluding Japan and certain other Asian countries) to develop and commercialize relugolix. Myovant is developing relugolix as an oral, once-daily, potential best-in-class GnRH receptor antagonist for uterine fibroids, endometriosis, and prostate cancer.