estradiol (TX 12-003HR) / TherapeuticsMD - LARVOL DELTA

[VIRTUAL] REPLENISH Trial: Endometrial Protection with a 17β-Estradiol and Progesterone Combination (TX-001HR) in Postmenopausal Women with Vasomotor Symptoms (ISGE-I 2020) - P3 | "Introduction: TX-001HR (approved as Bijuva® in the US, TherapeuticsMD, Inc., Boca Raton, FL) is a hormone therapy (HT) of combined naturally occurring 17β-estradiol and progesterone (which some call bio-identical) in a single, oral softgel capsule developed to treat menopause-related vasomotor symptoms (VMS). TX-001HR had a safe endometrial profile in postmenopausal women seeking relief for VMS. No endometrial hyperplasia or malignancy, or unexpected safety issues were observed, which is in contrast to what has been reported with compounded BHT. If approved, TX-001HR may be an alternative option of naturally occurring estradiol and progesterone that can be used to treat hot flushes for the estimated millions of postmenopausal women currently using unregulated, unapproved, compounded BHT, whose efficacy and safety have not been studied in rigorous clinical trials."

Clinical • Endometrial Cancer • Oncology • Solid Tumor • Women's Health

[VIRTUAL] REPLENISH trial: TX-001HR (17β-Estradiol and Progesterone Combination) Significantly Improved Moderate to Severe Hot Flushes in Postmenopausal Women (ISGE-I 2020) - P3 | "Introduction: TX-001HR (approved as Bijuva® in the US, TherapeuticsMD, Inc., Boca Raton, FL) is a hormone therapy (HT) of naturally occurring 17β-estradiol combined with progesterone (which some call bio-identical) in a single, oral softgel capsule developed to treat menopausal vasomotor symptoms (VMS). TX-001HR 1.0 mg/100 mg or 0.5 mg/100 mg effectively treated menopause-related moderate to severe hot flushes. If approved, TX-001HR – the first combination HT product containing naturally occurring 17β-estradiol and progesterone – may provide an alternative option for the estimated millions of women currently using unregulated, unapproved, compounded bio-identical HT."

Clinical

TX-004HR clinically improves symptoms of vulvar and vaginal atrophy in postmenopausal women. (PubMed, Climacteric) - "TX-004HR provided clinically meaningful improvements in dyspareunia and vaginal dryness associated with dyspareunia in postmenopausal women with VVA. Clinicians may be able to use this information when discussing patients' expectations regarding symptom improvement with the estradiol vaginal insert."

Clinical • Journal • Vaginal Atrophy

Early onset of action with a 17β-estradiol, softgel, vaginal insert for treating vulvar and vaginal atrophy and moderate to severe dyspareunia. (PubMed, Menopause) - "A high percentage of postmenopausal women with moderate to severe dyspareunia responded with the E2 softgel vaginal insert at week 2, and a positive response at week 2 predicted a positive response at week 12."

Journal • Vaginal Atrophy

[VIRTUAL] Progesterone Receptor Expression in Endometrial Biopsies After 12 Weeks of Exposure to A 4-µg E2 Softgel Vaginal Insert or Placebo (ENDO-I 2020) - "No meaningful difference in endometrial PR expression was observed with the vaginal 4-µg E2 insert at week 12. These data support our hypothesis and the assertion that low-dose, local vaginal E2 exposure with the insert placed in the lower part of the vagina, does not pose an endometrial safety issue in postmenopausal women."

Clinical • Vaginal Atrophy • PGR

REPLENISH: A Safety and Efficacy Study of the Combination Estradiol and Progesterone to Treat Vasomotor Symptoms (clinicaltrials.gov) - P3; N=1750; Active, not recruiting; Sponsor: TherapeuticsMD; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar

Progesterone Receptor Expression in Endometrial Biopsies After 12 Weeks of Exposure to A 4-µg E2 Softgel Vaginal Insert or Placebo (ENDO 2020) - "No meaningful difference in endometrial PR expression was observed with the vaginal 4-µg E2 insert at week 12. These data support our hypothesis and the assertion that low-dose, local vaginal E2 exposure with the insert placed in the lower part of the vagina, does not pose an endometrial safety issue in postmenopausal women."

Clinical • PGR

The Effects of Annovera™ and Tampon Co-Usage on the Pharmacokinetics of Segesterone Acetate and Ethinyl Estradiol (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: TherapeuticsMD; Not yet recruiting ➔ Recruiting

Enrollment open

Annovera™ Drug-Drug Interaction Study (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: TherapeuticsMD

New P1 trial

The Effects of Annovera™ and Tampon Co-Usage on the Pharmacokinetics of Segesterone Acetate and Ethinyl Estradiol (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: TherapeuticsMD

New P1 trial

Effect of Oral Estradiol and Progesterone Therapy on Vaginal Cytokines in Postmenopausal Women (clinicaltrials.gov) - P=N/A; N=30; Not yet recruiting; Sponsor: Intira Sriprasert; Initiation date: Aug 2014 ➔ Oct 2015; Trial primary completion date: Aug 2015 ➔ Oct 2016

Clinical • Trial initiation date • Trial primary completion date

Effect of Oral Estradiol and Progesterone Therapy on Vaginal Cytokines in Postmenopausal Women (clinicaltrials.gov) - P3; N=20; Completed; Sponsor: Intira Sriprasert; Recruiting ➔ Completed; Phase classification: PN/A ➔ P3; N=30 ➔ 20; Trial completion date: Aug 2017 ➔ Aug 2018; Trial primary completion date: Dec 2016 ➔ Aug 2018

Clinical • Enrollment change • Phase classification • Trial completion • Trial completion date • Trial primary completion date

Effect of Oral Estradiol and Progesterone Therapy on Vaginal Cytokines in Postmenopausal Women (clinicaltrials.gov) - P=N/A; N=30; Recruiting; Sponsor: Intira Sriprasert; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Effect of Oral Estradiol and Progesterone Therapy on Vaginal Cytokines in Postmenopausal Women (clinicaltrials.gov) - P=N/A; N=30; Not yet recruiting; Sponsor: Intira Sriprasert

Clinical

Estradiol vaginal inserts (4 µg and 10 µg) for treating moderate to severe vulvar and vaginal atrophy: a review of phase 3 safety, efficacy and pharmacokinetic data. (PubMed, Curr Med Res Opin) - P3; "The recently FDA-approved E2 softgel vaginal insert (4 µg and 10 µg) was safe and effective over 12 weeks for treating moderate to severe dyspareunia due to menopausal VVA with minimal systemic E2 levels."

Clinical • Journal • P3 data • PK/PD data

Early onset of action with a 17β-estradiol, softgel, vaginal insert for treating vulvar and vaginal atrophy and moderate to severe dyspareunia. (PubMed, Menopause) - "A high percentage of postmenopausal women with moderate to severe dyspareunia responded with the E2 softgel vaginal insert at week 2, and a positive response at week 2 predicted a positive response at week 12."

Journal

Contraceptive vaginal ring containing segesterone acetate and ethinyl estradiol: long-acting, patient-controlled, procedure-free, reversible prescription birth control. (PubMed, Drugs Today (Barc)) - "Because of this, the FDA has required a postmarketing study to determine the true incidence of this adverse effect. The CVR was developed by the Population Council, is known as Annovera, and will be marketed by TherapeuticsMD in the U.S."

Clinical • Journal

Uterine bleeding rates with hormone therapies in menopausal women with vasomotor symptoms (EMAS 2019) - P3; " Bleeding data were identified for Bijuva (E2/P4 [mg/mg] 1/100), Prempro ® (CEE/MPA [mg/mg] 0.625/5; 0.625/2.5; 0.45/1.5; 0.3/1.5), Activella ® (E2/NETA [mg/mg] 1/0.5; 0.5/0.1) Angeliq ® (E2/DRSP [mg/mg] 1/0.5), Climara Pro ® (E2/LNG [mg/mg] 0.045/0.015) and CombiPatch ® (E2/NETA [mg/mg] 0.05/0.14; 0.05/0.25). Comparing amenorrhea rates over time of E2/P4 from REPLENISH with those reported in published product information for other HT with synthetic progestins in separate studies, using different methodologies, suggests a potentially improved bleeding profile with E2/P4. Endometrial bleeding incidence with CHT products (other than in one survey) has not been published, even though many women choose to use them to treat their VMS."

Clinical

A 17β-estradiol, softgel, vaginal insert had an early onset of action for treating moderate to severe menopausal vulvar and vaginal atrophy (VVA) and Dyspareuni (EMAS 2019) - P3; "An early onset of action of the E2 softgel vaginal insert was observed based on a high proportion of responders with 2 weeks of treatment in menopausal women with moderate to severe dyspareunia. The likelihood of responding to therapy was also significantly greater in women who used the E2 vaginal insert versus placebo, and having a positive response to the E2 vaginal insert at week 2 strongly predicts a positive response with treatment at week 12."

Effects of estradiol and progesterone on sleep disturbance using mediation modeling (EMAS 2019) - P3; "The oral 1 mg 17β-estradiol/100 mg progesterone (E2/P4) softgel capsule (Bijuva TM ; TherapeuticsMD, Boca Raton, FL) was shown in REPLENISH to reduce moderate to severe hot flush (HF) frequency and severity and improve quality of life outcomes in postmenopausal women with a uterus, while protecting the endometrium. In REPLENISH, mediation modeling showed that E2/P4 improved sleep disturbances indirectly through improvements in HF symptoms and decreases in HF botherness (as measured by MENQOL). In women with moderate to severe VMS, oral E2/P4 capsules may also improve sleep."

Predictors Of Vaginal/Uterine Bleeding With Oral TX-001HR (Estradiol and Progesterone) Capsules Taken For Menopausal Vasomotor Symptoms (ENDO 2019) - P3; "...Cumulative amenorrhea rates (no bleeding or spotting for 13 cycles) ranging from 23% to 49% with current HT options1-3 are relatively lower than the 56% to 73% observed in the REPLENISH trial.4 The REPLENISH trial (NCT01942668) was a 12-month, phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR (bioidentical 17β-estradiol and progesterone [E2/P4] combined in a single, oral softgel capsule; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL) vs placebo in 1835 menopausal women (40−65 y; intact uterus) for the treatment of menopausal, moderate to severe vasomotor symptoms (VMS)...Prempro tablets PI...Activella tablets PI...Angeliq Tablets PI...Obstet Gynecol. 2018;132:161-170."

Predictors Of Vaginal/Uterine Bleeding With Oral TX-001HR (Estradiol and Progesterone) Capsules Taken For Menopausal Vasomotor Symptoms (ENDO 2019) - P3; "...Cumulative amenorrhea rates (no bleeding or spotting for 13 cycles) ranging from 23% to 49% with current HT options1-3 are relatively lower than the 56% to 73% observed in the REPLENISH trial.4 The REPLENISH trial (NCT01942668) was a 12-month, phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX-001HR (bioidentical 17β-estradiol and progesterone [E2/P4] combined in a single, oral softgel capsule; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL) vs placebo in 1835 menopausal women (40−65 y; intact uterus) for the treatment of menopausal, moderate to severe vasomotor symptoms (VMS)...Prempro tablets PI...Activella tablets PI...Angeliq Tablets PI...Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*"

Bioidentical Estradiol and Progesterone Improved Hot Flushes, Night Sweats and Sweating (ENDO 2019) - P3; "The objective of this analysis was to further determine the effects of the E2/P4 capsules versus placebo on vasomotor symptoms (VMS) as assessed by the menopause-specific quality of life (MENQOL) questionnaire.In the REPLENISH trial (NCT01942668), women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized 1:1:1:1:1 to daily E2/P4 (mg/mg) of 1/100 (FDA approved as BIJUVATM), 0.5/100, 0.5/50, 0.25/50, or placebo (VMS substudy). Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*"

Combined Bioidentical Estradiol and Progesterone Capsules Improved Quality of Sleep in Postmenopausal Women with Vasomotor Symptoms (ENDO 2019) - P3; "In the REPLENISH trial, the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4 FDA approved as BIJUVATM; TherapeuticsMD, Boca Raton, FL), was shown to reduce moderate to severe hot flush frequency and severity and improve quality of life outcomes in menopausal women with a uterus, while protecting the endometrium. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*"

Clinical

Nonsmokers Benefit from Lower Doses of an Estradiol/Progesterone Combination: Results of the REPLENISH Trial (ENDO 2019) - P3; "The 1 mg E2/100 mg P4 dose is FDA approved as BIJUVATM (TherapeuticsMD, Boca Raton, FL). Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO."

Late-breaking abstract