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40104711000001109

New Medicines

Ryeqo (UK/EU), Myfembree (US) Uterine fibroids

Information

Ryeqo (UK/EU), Myfembree (US)
New formulation
Gedeon Richter
Myovant Sciences

Development and Regulatory status

Launched
Approved (Licensed)
Approved (Licensed)
September 2021
Oct 21Price for Ryeqo = £72.00 for 28 film coated tablets [23].
Sep 21Ryeqo is available in the UK [22].
Aug 21Approved by MHRA for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. As per the EU approval, the MHRA have not stated a limit on duration of use [21].
Jul 21Approved in EU, with no limitation for duration of use, as supported by safety and efficacy data from the Phase 3 LIBERTY program [20]
May 21Approved in US, with a treatment duration of up to 24 months [19].
May 21Recommended for EU approval by CHMP – the full indication is ‘Ryeqo is indicated for treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age’. Ryeqo will be available as 40-mg/1-mg/0.5-mg film-coated tablets [18].
May 21EMA decision expected mid-21; Gideon Richter to launch and commercialise, if approved [17].
Jun 20Filed in US [14].
Apr 20Myovant announce plans to submit NDA for once-daily, oral relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) for women with heavy menstrual bleeding associated with uterine fibroids in May 2020 [12].
Mar 20Myovant have submitted a marketing application (MAA) to the EMA for relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) for the treatment of women with moderate to severe symptoms associated with uterine fibroids [11].
Nov 19Myovant now expect to file NDA with FDA April 20, and to file a MAA in EU Q1 20 [9].
Sep 19Myovant is expected to file for FDA approval by end of 2019/20 financial year [8].

Category

GnRH antagonist and low dose hormonal therapy
Uterine fibroids are the single most common indication for hysterectomy. They are clinically apparent in up to 25% of women. Treatment is only required if symptomatic, as long as other causes of pelvic masses and abnormal bleeding have been excluded. Expectant management is a valid option, especially in the peri-menopause [1].
Uterine fibroids
Oral

Further information

Yes

Trial or other data

Mar 21PIII LIBERTY randomised withdrawal study meets primary end point. Women who had competed LIBERTY long-term extension study were randomised at week 52 to once weekly relugolix combination therapy(ReCT) or placebo for 1 year; 78.4% who continued on ReCT achieved sustained responder rate (menstrual blood loss <80mL) vs 15.1% who discontinued treatment through week 76 [16].
Feb 21Two identical 24-week, PIII trials (NCT03049735, n=388 and NCT03103087, n=382) found once-daily relugolix, an oral gonadotropin-releasing hormone-receptor antagonist, in combination with estradiol & norethindrone acetate, resulted in significant reduction in menstrual bleeding vs placebo, & preserved BMD [15].
Feb 20Data from PIII LIBERTY extension study of once-daily, oral relugolix combination therapy in women with heavy menstrual bleeding associated with uterine fibroids shows an 88% one-year response rate. Women who received oral relugolix experienced an average 89.9% reduction in menstrual blood loss from baseline at 1 yr and bone mineral density was maintained through 1 year.[10]
Jul 19PIII LIBERTY 2 study meets primary endpoint, 71.2% of women who received once-daily relugolix combination therapy achieved responder criteria vs 14.7% of women receiving placebo [7].
May 19Data from PIII LIBERTY 2 study is expected Q3 2019. If results are positive, Myovant plan to submit a NDA to US FDA Q4 2019 [6].
May 19Myovant report positive data from PIII LIBERTY 1 study; 73.4% of patients receiving relugolix had a 50% decrease in blood loss, as well as reduction in blood loss to <80mL vs 18.9% receiving placebo [5].
Dec 18NCT03103087 due to complete primary data collection Sep 2019
Feb 18Filed in Japan [4]
Nov 17Positive top-line results from a PIII study (NCT02655224) of relugolix for treatment of pain associated with uterine fibroids announced. The RCT (n=65 in Japan) met the primary endpoint with 57.6% of women demonstrating a marked improvement in pain symptoms (maximum pain score of ≤ 1 on scale of 0-10) vs. 3.1% on placebo (p<0.0001) [3].
Mar 17PIII LIBERTY 2 trial to evaluate safety and efficacy of relugolix with and without low-dose hormonal add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids starts (MVT-601-3002; NCT03103087). It will enrol 390 patients in the US. Patients will be randomised to one of three groups: relugolix 40 mg orally once daily co-administered with low-dose hormonal add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate) for 24 weeks, relugolix 40 mg orally once daily monotherapy for 12 weeks followed by relugolix 40 mg once daily co-administered with hormonal add-back therapy for an additional 12 weeks, or placebo once daily for a period of 24 weeks. Primary efficacy outcome of the studies is a clinically-meaningful reduction in menstrual blood loss based upon the alkaline haematin method [2].
Jan 17 PIII LIBERTY 1 trial to evaluate safety and efficacy of relugolix with and without low-dose hormonal add-back therapy in women with heavy menstrual bleeding associated with uterine fibroids starts (MVT-601-3001; NCT03049735). It will enrol 390 patients in the US. Patients will be randomised to one of three groups: relugolix 40 mg orally once daily co-administered with low-dose hormonal add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate) for 24 weeks, relugolix 40 mg orally once daily monotherapy for 12 weeks followed by relugolix 40 mg once daily co-administered with hormonal add-back therapy for an additional 12 weeks, or placebo once daily for a period of 24 weeks. Primary efficacy outcome is a clinically-meaningful reduction in menstrual blood loss based upon the alkaline haematin method, a standardized centrally-assessed quantitative measurement of menstrual blood loss [2].

Evidence based evaluations

Information

Ryeqo (UK/EU), Myfembree (US)
Licence extension / variation
Gedeon Richter
Myovant Sciences

Development and Regulatory status

None
Phase III Clinical Trials
Pre-registration (Filed)
Sep 21US FDA accept NDA for Myfembree for treatment of moderate to severe pain associated with endometriosis and assign a PDUFA date of 6/5/22 [11].
May 21Company expect to submit MAA to EMA for relugolix combination tablet for the treatment of women with endometriosis-associated pain in 2021; Richter will be the MAA sponsor [10].
Jan 21Company re-announced plans to submit NDA to US FDA in H1 2021. They provide no indication as to their plans for filing in the EU/UK. [9]
Nov 20US filing for the treatment of women with endometriosis-associated pain expected in H1 2021. EU MAA submission to EMA expected in 2021. Gedeon Richter will be the MAA sponsor [8].
Mar 20Myovant enter into an exclusive license agreement with Richter for Richter to commercialize relugolix combination tablet for uterine fibroids and endometriosis in Europe [7].

Category

GnRH antagonist and low dose hormonal therapy
Endometriosis is estimated to affect 10-15% of women of reproductive age. However, it is difficult to determine the prevalence because of the diversity of symptoms and their severity and because endometriosis may be asymptomatic [2].
Endometriosis-related pain
Oral

Further information

Yes

Trial or other data

Jan 21Findings from a PIII long-term extension study (involving pts from SPIRIT trials) show relugolix with estradiol and norethindrone acetate leads to clinically meaningful reductions in menstrual pain and non-menstrual pelvic pain over one year in women with endometriosis. Over a year, a mean 82.8% reduction was seen on the 11-point Numerical Rating Scale (0-10) for dysmenorrhea from 7.4 (severe pain) to 1.3 (mild pain). Bone mineral density remained stable in all pts treated with the combination therapy and no new safety signals were found with the treatment compared with safety findings from the SPIRIT 1 and SPIRIT 2 studies. Commonly reported adverse events included headache, nasopharyngitis, and hot flashes. [9]
Jun 20Positive results from PIII SPIRIT 1 study announced. Co-primary endpoints were met with response rates of 74.5% vs. 26.9% and 58.5% vs 39.6% for menstrual pain and non-menstrual pelvic pain vs. placebo respectively [8].
Apr 20Results from Replicate PIII study expected in Q2 2020.[6]
Apr 20Positive results from PIII SPIRIT 2 study annouced. Co-primary endpoints were met with response rates of 75.2% vs. 30.4% (p < 0.0001) and 66.0% vs. 42.6% (p < 0.0001) for dysmenorrhea and non-menstrual pelvic pain vs. placebo respectively. Women receiving relugolix with estradiol 1.0 mg, and norethindrone acetate 0.5 mg once daily for 6 months, on average, reported reductions on the Numerical Rating Scale for dysmenorrhea from 7.2 (severe pain) to 1.7 (mild pain). Six key secondary endpoints were acheived including improvement in impact of pain on daily activities and a greater proportion of women not using opioids with a generally well-tolerated safety profile including minimal bone mineral density loss.[6]
Nov 19Top-line results from SPIRIT 2 and SPIRIT 1 are expected in the Q1 and Q2 2020, respectively [5].
Sep 19PIII study SPIRIT 2 has completed patient recruitment, this is the first of two replicate studies evaluating relugolix combination therapy in women with endometriosis-associated pain [4].
Dec 18NCT03204318 and NCT03204331 still due to complete Dec 19.
Nov 17Collection of primary outcome data in SPIRIT 1 and 2 is expected to complete in Dec 19 [3].
Nov 17PIII SPIRIT 1 (MVT-601-3101; NCT03204318) and SPIRIT 2 (MVT-601-3102; NCT03204331) trials were started in Jun 17 and Aug 17, respectively, to evaluate efficacy and safety of relugolix 40mg once daily in women with endometriosis-associated pain. Eligible women in each of the trials will be randomised to one of three groups: relugolix 40 mg orally once daily co-administered with low-dose hormonal add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate) for 24 weeks, relugolix 40 mg orally once daily monotherapy for 12 weeks followed by relugolix 40 mg once daily co-administered with hormonal add-back therapy for an additional 12 weeks, or placebo once daily for a period of 24 weeks. The primary endpoint will assess the proportion of women with reduction in dysmenorrhoea (menstrual pain) and the reduction in non-menstrual pelvic pain. Each randomised, double-blind, placebo-controlled trial will enrol approximately 600 women patients in the US. Eligible patients completing the initial 24-week blinded assessment will be offered an active treatment extension with relugolix 40 mg once daily co-administered with hormonal add-back therapy for an additional 28-week period, resulting in a total treatment period of up to 52 weeks, to evaluate the safety of longer-term treatment [1].

Ryeqo (UK/EU), Myfembree (US) Contraception in healthy women aged 18 to 35 years

Information

Ryeqo (UK/EU), Myfembree (US)
Licence extension / variation
Gedeon Richter
Myovant Sciences

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Fixed-dose combination of 1mg estradiol, 0.5mg norethisterone acetate and relugolix 40mg (a gonadotropin-releasing hormone receptor antagonist [GnRH])
75% of women aged 16-49 years use some type of contraception; 25% of women use the combined oral contraceptive pill (COCP) [1].
Contraception in healthy women aged 18 to 35 years
Oral