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. 2020 May 4;41(5):bnaa012. doi: 10.1210/endrev/bnaa012

Table 1.

Clinical efficacy of SPRMs in uterine fibroids, endometriosis, endometrial cancer, and breast cancer.

SPRMs Pathological Conditions Clinical Trial Treatment Dose Duration Clinical Efficacy Tolerability and Safety Concerns
Mifepristone Uterine fibroid Phase I (NCT00579475) 50 mg 3 months

  • - Close to 100% of women experience complete free of bleeding (125).

  • - Reduced fibroid volume by 28% compared to placebo (125).

  • - One patient had elevated levels of liver transferase enzyme profile (125).

  • - No evidence of hyperplasia or malignancy (125).

  • - Nonphysiological appearances were reported (125).

  • - Cystic glandular dilatation was present (125).
Phase II 10 mg 3 months

  • - Amenorrhea rates were 84.2% (124).

  • - Reduced uterine and fibroid volume by 26–30% (124).

  • - Endometrial hyperplasia without atypia was observed in 63.1% of women (124).
Phase II (NCT00881140) 10 mg (vaginal) 3 months

  • - Amenorrhea was 44.8% (287).

  • - Decreased UFS-QoL score from 20.7 to 14.0 (287).

  • - Reduced fibroid volume from 135 cc to 101.2 cc (287).

  • - Hot flashes were reported by 10.3%, nausea by 6.9%, feeling of weakness by 6.9%, abdominal pain by 24.1%, and vaginal discharge by 20.7% of cases (287).
Phase II 5 mg 3 months

  • - Amenorrhea was reported in 93.1% of cases (126).

  • - Reduced fibroid volume by 28.5% (126).

  • - Hot flashes were reported by 24.1% of cases (126).

  • - PAECs were reported in 24.5% on cases (126).
Phase II 5 mg or 10 mg 6 months and follow-up over 12 months

  • - Amenorrhea was 90.2% and 94.8% with 5 and 10 mg mifepristone, respectively (280).

  • - Reduced fibroid volume by 48.1% and 39.1% with 5 and 10 mg, respectively (280).

  • - Hepatic transaminases were elevated in 7.3% and 5.1% of patients in the 5 and 10 mg groups, respectively (280).

  • - 9.8% and 20.5% (hot flashes), 3.7% (nausea), 3.8% (vomiting), and 8.5% and 12.8% (feeling of fatigue) with 5 and 10 mg mifepristone dose, respectively, or either dose (280).

  • - PAECs were reported by 26.8% and 42.9% of women in 5 mg and 10 mg treated groups, respectively (280).
Phase III (NCT00133705) 5 mg 6 months

  • - Amenorrhea was occurred in 41% of cases (123).

  • - Uterine size was reduced by an average of 47% (123).

  • - No endometrial hyperplasia was noted (123).
Phase III (NCT01786226) 2.5 or 5 mg 3 months

  • - Amenorrhea was observed in 78.3% and 93.6% of women in 2.5 and 5 mg, respectively (285).

  • - Fibroid volume was decreased by 27.9% and 45.5%, with 2.5 and 5 mg, respectively (285).

  • - 9.4% and 15.6% (hot flashes), 1.9% and 3.7% (nausea), 3.8% and 2.7% (vomiting), 1.9% and 3.7% (feeling of fatigue) were observed in the 2.5 and 5 mg groups, respectively (285).

  • - Transaminases ASAT or ALAT or both were raised in 12.7% and 6.6% of women with 2.5 and 5 mg mifepristone, respectively (285).

  • - No evidence of endometrial hyperplasia was reported (285).
Endometriosis Phase I 5 or 100 mg 3–6 months

  • - Pelvic pain was improved (324).

  • - The regression of endometriosis was not evident (324).

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Phase I 50 mg 6 months

  • - There was a 55% mean regression in visible endometriosis (325).

  • - Improved pelvic pain and uterine cramping (325).

  • - Patient experienced higher levels of liver transaminases (325).
Phase I 5 mg 6 months

  • - Cyclic bleeding was ceased (327).

  • - Pelvic pain was improved (327).

  • - No significant change was observed in mean endometriosis score (327).

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Phase II/III (NCT02271958) 5 or 10 mg 6 months

  • - Dysmenorrhea was declined to 10.2%, 1.1%, and 1.1% with 2.5, 5, and 10 mg, respectively (326).

  • - Amenorrhea was reported in 78.7%, 97.8%, and 98.9% with 2.5, 5, and 10 mg, respectively (326).

  • - Hot flashes, nausea, vomiting, and fatigue/tiredness were reported (326).

  • - Hepatic transaminases up to 99 IU in 4% subjects (326).

  • - PAECs were reported in 19.7%, 9.7%, and 13.0% of patients with 2.5, 5, and 10 mg, respectively (326).
Endometrial cancer Phase II (NCT00505739) 200 mg 8 weeks to 2 years

  • - Overall, resulted in a 25% stable disease rate (337).

  • - No significant changes were observed in quality of life (337).

  • - Anorexia, fatigue, and mood alterations observed in 50%, 50%, and 58% of patients, respectively (337).
Breast cancer Phase II 200 mg 16 weeks

  • - Partial responses were observed in all patients (response rate 10.7%).

  • - Nausea, lethargy, anorexia, and hot flashes were reported (355).
Asoprisnil Uterine fibroid Phase II (NCT0016045) 5, 10, or 25 mg 12 weeks

  • - Suppressed uterine bleeding by 28%, 64%, and 83% with 5, 10, and 25 mg, respectively (292).

  • - Amenorrhea rates were 16%, 36%, and 70% at 5, 10, and 25 mg, respectively (292).

  • - Uterine volume was reduced by14%, 9%, and 17% at 5, 10, and 25 mg, respectively (292).

  • - Fibroid volume was reduced by 36% at 25 mg (292).

  • - Reduced bloating and pelvic pressure (292).

  • - Vasomotor symptoms were reported by 3%, 10%, and 8% at 5, 10, and 25 mg, respectively (292).

  • - No adverse endometrial effects, such as hyperplasia or neoplasms were detected (292).

  • - PAECs were detected in 43%, 58%, and 58% of women with 5, 10, and 25 mg, respectively (292).
Phase II 10 or 20 mg 12 weeks

  • - Uterine bleeding was suppressed by 33% and 91% of women with 10 and 25 mg, respectively (293).

  • - Fibroid volume was reduced by 0.4% and 25.8% with 10 and 25 mg, respectively (293).

  • - Headache, nasopharyngitis, nausea, back pain, perioperative complications, and abdominal pain were reported (293).
Phase III ((NCT00152269, NCT00160381) 10 or 25 mg 12 months

  • - Amenorrheic patients were 66–78% in 10-mg group and 83–93% in 25-mg group (294).

  • - Fibroid and uterine sizes were decreased by 48% and 28% with 10 mg and 63% and 39% with 25 mg (294).

  • - Significant improvements in HRQL were observed (294).

  • - Showed significant changes in endometrial thickness (~2 increased mm) (294).

  • - Adverse endometrial findings were observed: complex hyperplasia without atypia after 6 months at 10 mg, and with low-grade endometrial adenosarcoma after 9 months at 25 mg of asoprisnil treatment (294).
Endometriosis Phase II (NCT00160446) 5, 10, or 25 mg 12 weeks

  • - Reduced average daily combined pelvic pain/dysmenorrhea scores (328).

  • - Induced amenorrhea by 50%, 71%, and 93% with 5, 10, and 25 mg, respectively

  • - Adverse events were evenly distributed among treatment and placebo groups (328).
Phase II (NCT00160433) 0.5, 1.5, or 5 mg 3 months

  • - 5 mg was the only effective dose for pain relief in subjects with endometriosis compared to placebo (20).

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Telapristone Uterine fibroid Phase I/II 12.5, 25, or 50 mg 3 months

  • - Reduced fibroid size by 10.6%, 32.6%, and 40.3%, with 12.5, 25, or 50 mg, respectively (249).

  • - Reduced number and intensity of uterine bleeding days (249).

  • - Overall incidence rate of adverse events were lower in the telapristone acetate-treated subjects (249).
Endometriosis Phase II (NCT00958412) 25 mg 4 months —

  • - Terminated due to safety issue.
Phase II (NCT01728454) 6 or 12 mg 18 weeks

  • - Results have not been published yet.

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Phase II (NCT00556075) 25 or 50 mg 4 months —

  • - Terminated due to safety issue.
Ulipristal acetate Uterine fibroid Phase II (NCT00290251) 10 or 20 mg or placebo 90–120 days

  • - Fibroid volume was reduced by 36% and 21% with 10 and 20 mg UPA, respectively (311).

  • - Improved quality of life (311).

  • - Endometrial cystic hyperplasia without evidence of atypia was detected (311).
Phase II 2.5, 5, or 10 mg 84 days

  • - Amenorrhea rates were 81% and 90% with 5 and 10 mg, respectively (312).

  • - Endometrial hyperplasia was not detected (312).
Phase II 10 or 20 mg or placebo 12 weeks

  • - Decreased fibroid volume by 17% and 24% with 10 and 20 mg, respectively (313).

  • - Amenorrhea rates were 77% (313).

  • - Cystic glandular dilatation, simple hyperplasia, or complex hyperplasia without cellular atypia or endometrial intraepithelial neoplasia was detected (313).
Phase III, PEARL I (NCT00755755) 5 or 10 mg or placebo 13 weeks

  • - Controlled uterine bleeding by 91% and 92% with 5 and 10 mg UPA, respectively (103).

  • - Induced amenorrhea in 73% and 82% of women with 5 and 10 mg, respectively (103).

  • - Decreased fibroid volume by 21% and 12% in 5 and 10 mg, respectively

  • - Reduced uterine volume was achieved by 25% (103).

  • - Adverse events, hot flashes, headache and pain, discomfort, or tenderness in the breasts were not frequent (103).

  • - PAECs were observed in 62% and 57% of women with 5 and 10 mg, respectively (103).
Phase III, PEARL II (NCT00740831) 5 or 10 mg or placebo 3 months

  • - Controlled uterine bleeding in 90% and 98% of women, respectively (306).

  • - Regression of fibroid volume was observed in 36% and 42% of women with 5 and 10 mg, respectively (306).

  • - Hot flashes (moderate to severe) were reported in 11% and 10% of women with 5 and 10 mg, respectively (306).

  • - PAECs were observed in 58% and 59% of women with 5 and 10 mg, respectively (306).

  • - PAECs were low and similar in the 3 treatment groups (6–7%) (306).
Phase III, PEARL III (NCT01156857), and PEARL III extension (NCT01252069) 10 mg or placebo 12 months (four 3-month courses)

  • - Amenorrhea rates were 79%, 89%, 88%, and 90% in women after first, second, third, and fourth courses, respectively (238).

  • - Regression rates in the volume of the 3 largest fibroids were 45.1% and 72.1% in the PEARL III and PEARL III extension study, respectively (238).

  • - TEAEs that occurred in >5% of women were headache (16.3%), nasopharyngitis (6.7%), and abdominal pain (5.3%) (238).

  • - PAECs were reported in 26% and 25% of women after first and fourth courses, respectively (238).
Phase III, PEARL IV (NCT01629563) 5 or 10 mg Repeated 12 weeks

  • - Amenorrhea in 62% and 73% of women with 5 mg and 10 mg UPA, respectively (237).

  • - Reduced fibroid volume by 38% and 38% after first course, and 54% and 58% after second course with 5 and 10 mg, respectively (237).

  • - Improved pain and quality of life (237).

  • - Headaches and hot flashes were the most frequently reported adverse events (237).

  • - PAECs were observed by 16% and 19% of women, with 5 and 10 mg, respectively (237).
Phase III, PREMYA (NCT01635452) 5 mg 3 months with 12 months follow-up

  • - Symptomatic improvements were reported in 60% of patients (307).

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Phase III, VENUS I (NCT02147197) 5 or 10 mg or placebo 12 weeks with 12 weeks drug-free follow-up

  • - Amenorrhea rates were 47.2% and 58.3% in the 5 and 10 mg groups, respectively (309).

  • - Reduced fibroid volume by 9.6% and 16.3% with 5 and 10 mg, respectively, after 3 months of treatment (309).

  • - After follow-up period, fibroid volume was decreased by 2.3% and 17.4% in the 5 and 10 mg, respectively (309).

  • - Common TEAEs were hot flashes, blood creatine phosphokinase elevation, and hypertension (309).

  • - PAECs were reported in 26.2% and 29.7% with 5 and 10 mg, respectively after 3 months of treatment (309).

  • - PAECs were decreased by end of follow-up period: 19.0% with 5 mg and 12.1% with 10 mg (309).
Phase III, VENUS II (NCT02147158) 5 or 10 mg or placebo 12 weeks with 12 weeks drug-free follow-up

  • - Amenorrhea rates were reported by 42.0%, and 54.8% of women with 5 and 10 mg, respectively (308).

  • - Fibroid volume was reduced by 11.9% and 13.5% with 5 and 10 mg, respectively (308).

  • - TEAEs were reported by 46.6%, and 43.2% with 5 mg, 10 mg, respectively (308).

  • - Common TEAEs were hot flashes, headache, fatigue, and nausea (308).

  • - PAECs were similar among treatment groups at baseline and after each treatment course (308).
Endometriosis Phase IV (NCT02213081) 15 mg 3 months

  • - Improved pain symptoms (331).

  • - PAECs were reported (331).
Vilaprisan Uterine fibroid Phase I (NCT01816815) 0.1, 0.5, 1, 2, or 5 mg 12 weeks

  • - Nonbleeding rates were 100% and 90.9% in 2 and 5 mg, respectively (317).

  • - Changes in endometrial thickness were not reported (317).

  • - No serious TEAEs or study discontinuations due to adverse events were reported (317).
Phase I (NCT02262663) 0.5, 1, 2, or 4 mg 12 weeks

  • - Amenorrhea occurred in 75% of patients during treatment at dosages ≥1 mg (318).

  • - PAEC features were dose-dependently increased, reaching values between 70% and 95% after doses ≥1 mg of vilaprisan (318).
Phase II, ASTEROID 1 (NCT02131662) 0.5, 1, 2, or 4 mg or placebo 12 weeks

  • - Induced amenorrhea in >83% of women with ≥1.0 mg (319).

  • - Fibroid volume was reduced by 14.9–41.4% (319).

  • - PAECs were observed in 33–58% of women (319).

  • - Most frequent TEAEs were ovarian cysts (11.0%), headache (9.7%), and hot flashes (9.3%) (319).

  • - Three women discontinued the study due to TEAEs (319).