pyrimidinones and Leiomyoma

What is this summary about? This is a summary of a research study (known as a clinical trial) called the LIBERTY extension study. The LIBERTY extension study is a long-term study looking at how well a medicine called relugolix combination therapy worked in reducing blood loss during menstrual periods in women with uterine fibroids with heavy menstrual periods. Women were included in the extension study if they finished the 24-week LIBERTY 1 or LIBERTY 2 studies. Heavy menstrual periods were considered to be menstrual blood loss of about one-third of a cup of blood (80 ml) per cycle for two cycles or about two-thirds of a cup of blood (160 ml) during one cycle. The LIBERTY extension study also looked at whether relugolix combination therapy was safe to take for up to 1 year. What were the results? Out of 770 total women with uterine fibroids with heavy menstrual bleeding who took part in the LIBERTY 1 and LIBERTY 2 studies, 476 took part in the LIBERTY extension study. From the start of the LIBERTY 1 and LIBERTY 2 studies through the end of the LIBERTY extension: 163 women took relugolix combination therapy for 52 weeks 149 women took relugolix alone for 12 weeks followed by relugolix combination therapy for 40 weeks 164 women took placebo for 24 weeks followed by relugolix combination therapy for 28 weeks The LIBERTY extension study showed that most women in all three treatment groups responded to relugolix combination therapy by having less bleeding during their menstrual periods, having improved anemia symptoms, and having stable bone mineral loss. Side effects were similar across treatment groups, and the most common side effects were headaches and hot flushes. What do the results mean? Women with uterine fibroids with heavy menstrual bleeding taking relugolix combination therapy may have fewer uterine fibroid bleeding symptoms for up to 1 year of treatment.

Topics: Clinical Trials as Topic; Female; Humans; Leiomyoma; Menorrhagia; Pyrimidinones; Uterine Neoplasms

Uterine fibroids (UF) are benign tumors common in premenopausal women, with strong impact on the health-care systems. For many years, surgery represented the only therapy for symptomatic fibroids. However, clinicians are observing a switch from surgery to noninvasive methods; in particular, medical treatment has been shown to be efficacious in obtaining a bleeding reduction and in ameliorating patient conditions.. The authors review the current options available for the treatment of women with UF, with a special focus on the newest one, relugolix. It is an orally active non-peptide Gonadotropin-releasing hormone (GnRH)-receptor antagonist recently licensed for women with symptomatic fibroids. Relugolix is a well-tolerated safe drug; it is effective in inducing a dose-dependent decrease in menstrual blood loss, with faster reduction of heavy menstrual bleeding (HMB) and a greater shrinkage in fibroid volume compared to the current standard of GnRH agonist treatment.. Relugolix is a promising drug for the non-surgical treatment of women with UF. To date, the only published data come from a well-selected Japanese female population study while results from worldwide ongoing studies are ongoing in order to confirm the efficacy of this GnRH agonist receptor.

Topics: Female; Humans; Hysterectomy; Leiomyoma; Menstruation; Phenylurea Compounds; Premenopause; Pyrimidinones; Randomized Controlled Trials as Topic; Receptors, LHRH; Treatment Outcome; Uterine Neoplasms

To assess the effect of once-daily relugolix combination therapy (relugolix-CT: relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) compared with placebo on moderate-to-severe pain in women with uterine leiomyomas and heavy menstrual bleeding.. Two replicate, multinational, double-blind, 24-week, randomized, phase 3 studies (LIBERTY 1 and 2) were conducted in premenopausal women with uterine leiomyoma-associated heavy menstrual bleeding (80 mL or greater per cycle for two cycles or 160 mL or greater during one cycle). A predefined secondary objective was to determine the effect of relugolix-CT on moderate-to-severe uterine leiomyoma-associated pain in the pain subpopulation (women with maximum pain scores of 4 or higher on the 0-10 numerical rating scale at baseline, with pain score reporting compliance of 80% (ie, 28 days or more over the last 35 days of treatment). This key secondary endpoint was defined as the proportion of women achieving minimal-to-no uterine leiomyoma-associated pain (maximum numerical rating scale score 1 or lower) at week 24; menstrual and nonmenstrual pain were evaluated in prespecified secondary analyses. Treatment comparisons were performed in the pooled LIBERTY 1 and 2 pain subpopulation using the Cochran-Mantel-Haenszel test stratified by baseline menstrual blood loss volume.. Across both trials, 509 women were randomized to relugolix-CT or placebo (April 2017-December 2018). Of these, 277 (54.4%) met pain subpopulation requirements. With relugolix-CT, 45.2% (95% CI 36.4-54.3) of women achieved minimal-to-no pain compared with 13.9% (95% CI 8.8-20.5) with placebo (nominal P<.001). The proportions of women with minimal-to-no pain during menstrual days and during nonmenstrual days were significantly higher with relugolix-CT (65.0% [95% CI 55.6-73.5] and 44.6% [95% CI 32.3-57.5], respectively) compared with placebo (19.3% [95% CI 13.2-26.7], nominal P<.001, and 21.6% [95% CI 12.9-32.7], nominal P=.004, respectively).. Over 24 weeks, relugolix-CT significantly reduced moderate-to-severe uterine leiomyoma-associated pain with a more pronounced effect on menstrual pain. These data support that relugolix-CT had clinically meaningful effects on women's experience of uterine leiomyoma-associated pain.. ClinicalTrials.gov: LIBERTY 1, NCT03049735; LIBERTY 2, NCT03103087.. Myovant Sciences GmbH.

Topics: Female; Freedom; Humans; Leiomyoma; Menorrhagia; Pelvic Pain; Phenylurea Compounds; Pyrimidinones; Randomized Controlled Trials as Topic; Uterine Neoplasms

In the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.. Women with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders ). Analyses were conducted for all three randomized treatment groups from pivotal studies.. Overall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma-associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.. Improvements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma-associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.. ClinicalTrials.gov , NCT03049735; NCT03103087; NCT03412890.. Myovant Sciences GmbH.

Topics: Female; Humans; Leiomyoma; Menorrhagia; Pyrimidinones; Uterine Neoplasms

Uterine leiomyomas are the most common neoplasm affecting women and frequently cause heavy menstrual bleeding and pain. Gonadotropin-releasing hormone (GnRH) receptor antagonists provide fast symptom relief and show promise as a medical (non-surgical) treatment option and as a presurgical treatment to reduce leiomyoma size. The aim of this study was to evaluate the efficacy and safety of three dose levels of oral relugolix, a small molecule GnRH receptor antagonist, in Japanese women with uterine leiomyomas and heavy menstrual bleeding.. This phase 2, multicenter, double-blind, parallel-group study was conducted at 36 sites in Japan in women with uterine leiomyomas and heavy menstrual bleeding, defined as a pictorial blood loss assessment chart (PBAC) score of ≥ 120 in one menstrual cycle. Patients were randomized 1:1:1:1 to relugolix 10, 20, or 40 mg, or placebo, orally once daily for 12 weeks. The primary endpoint was the proportion of patients with a total PBAC score of < 10 from week 6 to 12. A sample size of 50 patients per group was estimated to provide ≥ 95% power, based on the comparison of relugolix 40 mg with placebo using a chi-square test with a significance level of 5% (two-sided).. From November 2011 to September 2012, 216 patients were randomized and 214 patients (99.1%) were analyzed. The proportion (difference vs. placebo) of patients that achieved the primary endpoint in the placebo and 10-, 20-, and 40-mg relugolix groups were 0%, 20.8% (95% confidence interval [CI]: 9.3-32.3, P < .001), 42.6% (95% CI: 29.4-55.8, P < .001), and 83.3% (95% CI: 73.4-93.3, P < .001), respectively. Though treatment-emergent adverse events were similar between the 20- and 40-mg groups, the incidence rates were more frequent compared with the placebo group. Most of these adverse events were mild or moderate in intensity.. Relugolix decreased menstrual blood loss in women with uterine leiomyomas in a dose-response manner, and was generally well tolerated.. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01452659 , NCT01452659 (registered 17/10/2011); JAPIC Clinical Trial Information, https://www.clinicaltrials.jp , JapicCTI-111590 (registered 31/08/2011).

Topics: Female; Humans; Leiomyoma; Menorrhagia; Phenylurea Compounds; Pyrimidinones; Treatment Outcome; Uterine Neoplasms

Uterine fibroids are a common cause of heavy menstrual bleeding and pain. Treatment with the combination of relugolix (an oral gonadotropin-releasing hormone-receptor antagonist), estradiol, and norethindrone acetate, administered once daily, may have efficacy in women with uterine fibroids and heavy bleeding while avoiding hypoestrogenic effects.. We conducted two replicate international, double-blind, 24-week, phase 3 trials involving women with fibroid-associated heavy menstrual bleeding. Participants were randomly assigned in a 1:1:1 ratio to receive once-daily placebo, relugolix combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate), or delayed relugolix combination therapy (40 mg of relugolix monotherapy, followed by relugolix combination therapy, each for 12 weeks). The primary efficacy end point in each trial was the percentage of participants with a response (volume of menstrual blood loss <80 ml and a ≥50% reduction in volume from baseline) in the relugolix combination therapy group, as compared with the placebo group. Key secondary end points were amenorrhea, volume of menstrual blood loss, distress from bleeding and pelvic discomfort, anemia, pain, fibroid volume, and uterine volume. Safety and bone mineral density were assessed.. A total of 388 women in trial L1 and 382 in trial L2 underwent randomization. A total of 73% of the participants in the relugolix combination therapy group in trial L1 and 71% of those in trial L2 had a response (primary end point), as compared with 19% and 15%, respectively, of those in the placebo groups (P<0.001 for both comparisons). Both relugolix combination therapy groups had significant improvements, as compared with the placebo groups, in six of seven key secondary end points, including measures of menstrual blood loss (including amenorrhea), pain, distress from bleeding and pelvic discomfort, anemia, and uterine volume, but not fibroid volume. The incidence of adverse events was similar with relugolix combination therapy and placebo. Bone mineral density was similar with relugolix combination therapy and placebo but decreased with relugolix monotherapy.. Once-daily relugolix combination therapy resulted in a significant reduction in menstrual bleeding, as compared with placebo, and preserved bone mineral density in women with uterine fibroids. (Funded by Myovant Sciences; LIBERTY 1 [L1] and LIBERTY 2 [L2] ClinicalTrials.gov numbers, NCT03049735 and NCT03103087, respectively.).

Topics: Adult; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Estradiol; Estrogens; Female; Hot Flashes; Humans; Leiomyoma; Menorrhagia; Middle Aged; Norethindrone Acetate; Phenylurea Compounds; Pyrimidinones; Uterine Neoplasms; Young Adult

To investigate the efficacy and safety of the oral gonadotropin-releasing hormone receptor antagonist, relugolix, in patients experiencing uterine fibroid-associated pain.. Phase 3, multicenter, randomized, double-blind, placebo-controlled study.. Medical centers.. Premenopausal Japanese women (N = 65) experiencing moderate-to-severe uterine fibroid-associated pain with a maximum Numerical Rating Scale (NRS) score of ≥4 were randomized and completed the study.. Once-daily 40 mg relugolix (n = 33) or placebo (n = 32) for 12 weeks.. Primary end point: proportion of patients with a maximum NRS score of ≤1 during the 28-day period before the final dose of study drug. Secondary end points: proportion of patients with no pain (NRS = 0) and percentage of days without pain during the 28-day period before the final dose of study drug; adverse events.. More patients receiving relugolix versus placebo achieved a maximum NRS score of ≤1 during the 28-day period before the final dose of study drug (57.6% vs. 3.1%). Similarly, more patients receiving relugolix versus placebo achieved a maximum NRS score of 0 (48.5% vs. 3.1%) and experienced more days without pain (96.4% vs. 71.4%). More patients receiving relugolix versus placebo experienced treatment-emergent adverse events (TEAEs; 87.9% vs. 56.3%); however, the rate of treatment discontinuation was low and not different between groups. Most TEAEs were mild to moderate in intensity. TEAEs (≥10%) included hot flush, metrorrhagia, hyperhidrosis, and menorrhagia, consistent with relugolix's mechanism of action, and viral upper respiratory tract infection.. Relugolix improved uterine fibroid-associated pain and was well tolerated.. NCT02655224.. JapicCTI-163127.

Topics: Administration, Oral; Adult; Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Humans; Japan; Leiomyoma; Middle Aged; Pelvic Pain; Phenylurea Compounds; Pyrimidinones; Treatment Outcome

To investigate the noninferiority of relugolix compared with leuprorelin acetate in reducing heavy menstrual bleeding associated with uterine leiomyomas.. In a double-blind, double-dummy trial, premenopausal women with uterine leiomyomas and heavy menstrual bleeding defined as a pictorial blood loss assessment chart score of at least 120 were randomized in a 1:1 ratio to relugolix (40 mg, oral, once daily) or leuprorelin acetate (1.88 mg or 3.75 mg, monthly injection) for 24 weeks. The primary endpoint was the proportion of patients with a total pictorial blood loss assessment chart score of less than 10 for weeks 6-12. Secondary endpoints included myoma and uterine volumes, and hemoglobin levels. A sample size of 144 patients per group (n=288) was estimated to provide at least 90% power to demonstrate noninferiority (prespecified noninferiority margin -15%; one-sided 0.025 level of significance).. From March 2016 to September 2017, 281 patients were randomized (relugolix, n=139, leuprorelin n=142). Demographic and baseline characteristics were well balanced; mean pictorial blood loss assessment chart score was 254.3 in the relugolix group and 263.7 in the leuprorelin group. The proportion of patients with total pictorial blood loss assessment chart score of less than 10 for weeks 6-12 was 82.2% in the relugolix group and 83.1% in the leuprorelin group, demonstrating noninferiority of relugolix compared with leuprorelin (relugolix-leuprorelin difference -0.9%; 95% CI: -10.10 to 8.35; prespecified noninferiority margin -15%; P=.001). Reductions in myoma and uterine volumes and increases in hemoglobin levels were comparable in the two groups. Relugolix was associated with an earlier effect on menstrual bleeding than leuprorelin (pictorial blood loss assessment chart score of less than 10, 64.2% vs 31.7% [relugolix-leuprorelin difference 32.5%; 95% CI: 20.95-44.13%] for weeks 2-6 and pictorial blood loss assessment chart score of 0, 52.6% vs 21.8% [30.7%; 95% CI: 19.45-42.00%] for weeks 2-6) and faster recovery of menses after treatment discontinuation (relugolix median [Q1, Q3], 37 days [32.0, 46.0]; leuprorelin median, 65 days [54.0, 77.0]). Adverse events and bone mineral density loss were similar between relugolix and leuprorelin treatment groups.. In women with uterine leiomyomas, once-daily treatment with relugolix, an oral gonadotropin-releasing hormone antagonist, demonstrated noninferiority to monthly leuprorelin for improvement of heavy menstrual bleeding at 6-12 weeks of treatment, had a more rapid effect on menstrual bleeding, and was generally well tolerated.. ClinicalTrials.gov, NCT02655237; JAPIC Clinical Trial Information, JapicCTI-163128.. Takeda Pharmaceutical Company Limited and an affiliate of NovaQuest Capital Management LLC.

Topics: Administration, Oral; Adult; Antineoplastic Agents, Hormonal; Double-Blind Method; Female; Gonadotropin-Releasing Hormone; Hemoglobins; Humans; Injections; Leiomyoma; Leuprolide; Menorrhagia; Middle Aged; Organ Size; Phenylurea Compounds; Pyrimidinones; Severity of Illness Index; Tumor Burden; Uterine Neoplasms; Uterus

Uterine fibroids (UF) are common benign tumors in women and are an important health concern in the US and globally. UF can severely compromise a woman's quality of life, thus making it an important health issue. In this podcast, a professor of Obstetrics and Gynecology, University of Chicago (Dr. Ayman Al-Hendy) and the CEO of the Fibroid Foundation (Sateria Venable) provide their perspectives on the diagnosis and management of UF, including common treatments (e.g., myomectomy or hysterectomy). They also discuss Relugolix combination therapy for UF, noting who could benefit from this treatment and how it works. Podcast audio available for this article.

Topics: Female; Humans; Hysterectomy; Leiomyoma; Pregnancy; Pyrimidinones; Quality of Life; Uterine Neoplasms

Uterine Fibroids (UFs) are the most predominant benign tumor in women who are coming of reproductive age, and causes intense economic load priced in billions of US dollars. Historically, surgery has been the main definitive treatment, albeit less attractive nowadays, especially for women with future fertility plans. Therefore, studies to explore the pharmacological treatment options are increasing especially as those that are currently available are limited for short-term use only.. This drug evaluation features the clinical results from previous and ongoing studies of relugolix, in combination with the add back therapy of estradiol (E2) and norethindrone acetate (NETA), as a novel, orally administered, nonpeptide antagonist of gonadotropin-releasing hormone (GnRH) for the management of heavy menstrual bleeding (HMB) in premenopausal women with UFs.. The combination of relugolix/E2/NETA is an encouraging, well-tolerated and noninvasive pharmacological option for UFs patients. Relugolix induced a concentration-dependent decrease in HMB. However, it should be used with hormonal add-back therapy (E2+ NETA) to avoid induced hypoestrogenic side effects, importantly bone mineral density loss. Moreover, symptoms will likely resume shortly after the termination of the relugolix combination administration.

Topics: Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Menorrhagia; Norethindrone Acetate; Phenylurea Compounds; Pyrimidinones; Uterine Neoplasms

To investigate the efficacy of short-term administration of relugolix, a novel orally active gonadotropin-releasing hormone (GnRH) antagonist, before single-port laparoscopic-assisted vaginal hysterectomy (LAVH) for symptomatic uterine myomas, retrospectively compared with injection of leuprorelin, a GnRH agonist.. A retrospective comparative study of each 35 women with symptomatic myomas in the relugolix and leuprorelin groups.. Before administration of relugolix and leuprorelin, the median uterine volume did not differ significantly between the two groups (p = 0.53). Median uterine volume change from baseline after short-term administration of relugolix and leuprorelin did not differ significantly (p = 0.17). Surgical duration (p = 0.84) and estimated blood loss (p = 0.48) were not different between the two groups. According to a patient questionnaire, the side effects of the drugs were not different between the two groups (p = 0.27). When patients were was asked if they wanted to have either of these drugs again, some relugolix users preferred leuprorelin due to concern about forgetting daily medication, while some leuprorelin users preferred relugolix to avoid pain at injection.. Oral relugolix medication or leuprorelin injection administered before single-port LAVH for uterine myomas yielded an equivalent reduction of uterine volume and perioperative outcomes with no significant adverse events. Patient preference for either oral daily relugolix or a monthly injection of leuprorelin could be considered when preoperative management is determined.

Topics: Female; Humans; Hysterectomy, Vaginal; Laparoscopy; Leiomyoma; Leuprolide; Myoma; Phenylurea Compounds; Pyrimidinones; Retrospective Studies; Uterine Neoplasms

Topics: Female; Freedom; Humans; Leiomyoma; Pain; Phenylurea Compounds; Pyrimidinones; Randomized Controlled Trials as Topic; Uterine Neoplasms

To determine the effect relugolix and elagolix have on the production of extracellular matrix (ECM) proteins in human leiomyoma cells.. Laboratory study.. University hospital.. None. January 5, 2022 Cell culture, protein analysis, immunohistochemistry.. Production of GnRHR, COL1A1, FN1, VCAN, p-ERK, & ERK in treated/untreated leiomyoma cells.. 100 nM relugolix resulted in decreased production of COL1A1 at 24 (1.78 0.06-fold; P < .05) and 48 hours (1.92 0.14-fold; P < .05). Elagolix treatment resulted in a decrease in COL1A1 production at 24 but not 48 hours. In 2D and 3D, 100 nM relugolix resulted in decreased production of FN1 at 24 (1.7 ± 0.07-fold; P < .05) and 48 hours (1.8 ± 0.07-fold; P < .05); 100 nM elagolix resulted in decreased production of FN1 at 24 (1.7 ± 0.14-fold; P < .05) and 48 hours (2.0 ± 0.09-fold; P < .05). For cells treated with relugolix 100 nM resulted in decreased VCAN production by 48 hours (0.66 ± 0.07-fold; P < .05). Contrary to our 3D data, 2D elagolix-treated cells demonstrated a decrease in VCAN production that was identified only at 24 hours. For GnRHR, no significant difference between the drugs was seen at 24 hours; at 48 hours production was only significantly decreased for relugolix (P < .05). Comparing both drugs, there was a significant difference in the concentration of p-ERK to ERK at 24 hours (P < .05); there was no difference by 48 hours.. Our findings demonstrated that treatment with either drug can 1) decrease ECM protein production and 2) inhibit the MAPK pathway.

Topics: Cell Culture Techniques, Three Dimensional; Extracellular Matrix; Extracellular Matrix Proteins; Female; Humans; Hydrocarbons, Fluorinated; Leiomyoma; Phenylurea Compounds; Pyrimidines; Pyrimidinones; Uterine Neoplasms

Topics: Drug Approval; Drug Combinations; Estradiol; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Leiomyoma; Menorrhagia; Norethindrone Acetate; Phenylurea Compounds; Pyrimidinones; United States; United States Food and Drug Administration

Topics: Humans; Leiomyoma; Phenylurea Compounds; Pyrimidinones

Recently, relugolix, an oral gonadotropin-releasing hormone receptor antagonist, has been considered an effective therapy for leiomyoma based on a phase 3 study in Japanese women. Leiomyoma combined with severe adenomyosis occasionally occurs in perimenopausal women; however, little information on the effectiveness of relugolix against severe adenomyosis exists.. A 49-year-old woman was referred to our hospital with acute lower abdominal pain and abnormal uterine bleeding. Magnetic resonance imaging revealed multiple leiomyomas with diffuse adenomyosis. Left hydrosalpinx was also observed. The patient refused surgical treatment and preferred oral relugolix. Since she experienced a hot flush and headache induced by relugolix, a traditional Japanese Kampo, kamishoyosan, was added to improve the side effects of relugolix. The patient was asymptomatic at the time of this report and experienced a significant shrinkage in uterine volume. Ultimately, she avoided hysterectomy as desired.. To our knowledge, this is the first report of co-occurring adenomyosis and leiomyoma, which was effectively treated with relugolix. Although the management of adverse side effects, including hot flush and headache by relugolix, has recently attracted attention and controversy, relugolix add-on therapy with kamishoyosan may help treat menopausal symptoms.

Topics: Adenomyosis; Female; Humans; Leiomyoma; Middle Aged; Phenylurea Compounds; Pyrimidinones; Uterine Neoplasms

Uterine leiomyomas represent the most common form of benign gynecological tumors affecting 20-40% of women during their life. Several therapeutic options are available for treating these patients. The use of medical treatment for myomas has largely grown in the last years, in particular for women who would refuse, postpone or are not candidates for surgery. In the last years, the clinical investigation of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ants) has emerged. This class of drugs exerts pure competitive antagonistic activity on the GnRH receptor at the pituitary gland, producing an immediate stop in the release of gonadotropins and sex steroids. Relugolix is an orally active nonpeptide GnRH-ant, recently licensed for marketing in Japan for the treatment of symptoms related to uterine myomas. Currently, several phase III clinical trials are ongoing to evaluate this molecule in this setting in the U.S. and Europe.

Topics: Female; Humans; Leiomyoma; Phenylurea Compounds; Pyrimidinones; Uterine Neoplasms

Topics: Female; Gonadotropin-Releasing Hormone; Humans; Japan; Leiomyoma; Pain; Phenylurea Compounds; Pyrimidinones

The orally active nonpeptide gonadotropin-releasing hormone (GnRH)-receptor antagonist relugolix (Relumina) is being developed by Takeda and ASKA Pharmaceutical as a treatment for various sex hormone related disorders. Relugolix was recently approved for marketing in Japan as a treatment for symptoms associated with uterine fibroids, and studies evaluating the efficacy of the drug as treatment for endometriosis-associated pain and prostate cancer are currently underway. This article summarizes the milestones in the development of relugolix leading to this first approval for the treatment of symptoms associated with uterine fibroids.

Topics: Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Drug Approval; Endometriosis; Female; Hormone Antagonists; Humans; Japan; Leiomyoma; Male; Middle Aged; Phenylurea Compounds; Prostatic Neoplasms; Pyrimidinones; Receptors, LHRH; Treatment Outcome