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TherapeuticsMD Announces Positive Top-Line Results from Pivotal Phase 3 Replenish Trial in Postmenopausal Women with Moderate to Severe Vasomotor Symptoms (VMS) Treated with TX-001HR
6 hours 10 minutes ago - DJNF
- TX-001HR, the first bio-identical combination therapy of estradiol and progesterone evaluated in a randomized, controlled clinical trial met all co-primary efficacy and safety endpoints at multiple doses -

- TX-001HR, if approved, offers a potential new alternative for millions of post-menopausal women currently using unapproved compounded hormone therapy for the treatment of VMS -

- Conference call today at 4:30 p.m. ET to discuss results -

BOCA RATON, Fla.--(BUSINESS WIRE)--December 05, 2016--

TherapeuticsMD, Inc. (NYSE MKT: TXMD), an innovative women's healthcare company, today announced positive top-line results from its pivotal phase 3 Replenish Trial of TX-001HR, an investigational bio-identical hormone therapy combination of 17ß-estradiol and progesterone in a single, oral softgel, for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause in post-menopausal women with an intact uterus.

This Smart News Release features multimedia. View the full release here: http://www.businesswire.com/news/home/20161205006226/en/

Figure 1. Mean Change from Baseline in Weekly Frequency of Moderate to Severe Hot Flashes for Weeks 1 to 12 (Graphic: Business Wire)

The Replenish Trial evaluated four doses of TX-001HR and placebo in 1,835 post-menopausal women between 40 and 65 years old. The doses studied were:

-- 17ß-estradiol 1 mg/progesterone 100 mg (n = 416)

-- 17ß-estradiol 0.5 mg/progesterone 100 mg (n = 423)

-- 17ß-estradiol 0.5 mg/progesterone 50 mg (n = 421)

-- 17ß-estradiol 0.25 mg/progesterone 50 mg (n = 424)

-- Placebo (n = 151)

The Replenish Trial results demonstrated:

-- TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5

mg/progesterone 100 mg both achieved all four of the co-primary efficacy

endpoints and the primary safety endpoint.

-- TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5

mg/progesterone 100 mg both demonstrated a statistically significant and

clinically meaningful reduction from baseline in both the frequency and

severity of hot flashes compared to placebo.

-- TX-001HR estradiol 0.5 mg/progesterone 50 mg and TX-001HR estradiol 0.25

mg/progesterone 50 mg were not statistically significant at all of the

co-primary efficacy endpoints. The estradiol 0.25 mg/progesterone 50 mg

dose was included in the clinical trial as a non-effective dose to meet

the recommendation of the FDA guidance to identify the lowest effective

dose.

-- The incidence of consensus endometrial hyperplasia or malignancy was 0

percent across all four TX-001HR doses, meeting the recommendations

established by the U.S. Food and Drug Agency's (FDA) draft guidance.1

As outlined in the FDA guidance, the co-primary efficacy endpoints in the Replenish Trial were the change from baseline in the number and severity of hot flashes at weeks 4 and 12 as compared to placebo.(1) The primary safety endpoint was the incidence of endometrial hyperplasia with up to 12 months of treatment. General safety was also evaluated.

The results of the Replenish Trial (p-values of < 0.05="" meet="" fda="" guidance="" and="" support="" evidence="" of="" efficacy)="" are="" summarized="" in="" the="" below="" table="" and="" included="" multimedia.="">

Replenish Trial Co-Primary Efficacy Endpoints: Mean Change in Frequency and

Severity of Hot Flashes Per

Week Versus Placebo at Weeks 4 and 12, VMS-MITT Population



1 mg/100 0.5 mg/100 0.5 mg/50 0.25 mg/50

Estradiol/Progesterone mg mg mg mg Placebo

(n = 141) (n = 149) (n = 147) (n = 154) (n = 135)



Frequency

Week 4 P-value versus

placebo <0.001 0.013="" 0.141="" 0.001="" -="">

Week 12 P-value versus

placebo <0.001><0.001 0.002=""><0.001 -="">



Severity

Week 4 P-value versus

placebo 0.031 0.005 0.401 0.100 -

Week 12 P-value versus

placebo <0.001><0.001 0.018="" 0.096="" -="">



Replenish Trial Primary Safety Endpoint: Incidence of Consensus Endometrial

Hyperplasia or Malignancy up to

12 months, Endometrial Safety Population( )

Endometrial Hyperplasia 0% (0/280) 0% (0/303) 0% (0/306) 0% (0/274) 0% (0/92)



MITT = Modified intent to treat

Per FDA, consensus hyperplasia refers to the concurrence of two of the three

pathologists be accepted as the final diagnosis(1)

P-value < 0.05="" meets="" fda="" guidance="" and="" supports="" evidence="" of="" efficacy="">

"We are very pleased that multiple doses of TX-001HR studied in the Replenish Trial demonstrated these positive results, suggesting that, if approved, this drug product candidate is poised to address the significant demand for bio-identical hormone therapy," said Chief Executive Officer Robert G. Finizio. "We have successfully advanced the science for post-menopausal women's health by finding a way to effectively combine bio-identical estradiol and bio-identical progesterone. The need for a bio-identical FDA-approved combination therapy has been unanswered for decades, driving women to use unapproved drugs mixed together by independent and community pharmacies that compound these products. We believe that TX-001HR, if approved, will provide women, healthcare providers and pharmacists with a proven safe, effective and insurance reimbursed bio-identical combination product, finally answering that need. We will continue to evaluate these promising data, and look forward to submitting a New Drug Application for TX-001HR to the Food and Drug Administration as early as the third quarter of 2017."

The trial also demonstrated a dose response favoring the higher doses of estradiol in combination with progesterone. The availability of multiple doses of TX-001HR would allow for individualized therapy to meet the needs of a diverse population of women.

The most common adverse events (>5 percent) reported on average in all the active treatment groups were headache, nasopharyngitis, breast tenderness, and upper respiratory infection. There was a very low reported incidence of adverse events of somnolence with TX-001HR, in contrast to commercially available oral progesterone where somnolence has been reported as a significant side effect. There were no unexpected safety signals.

The Replenish Trial evaluated various secondary endpoints using well-validated patient reported outcome tools, including the Menopause-Specific Quality of Life (MENQOL), the Clinical Global Impression scale (CGI), and the responder analysis rate. Both TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5 mg/progesterone 100 mg demonstrated clinically meaningful and statistically significant improvements in the secondary endpoints using these tools.

Additional efficacy and safety analyses of the Replenish Trial data are ongoing and TherapeuticsMD plans to submit the full Replenish Trial results for presentation at future scientific meetings and for publication in peer-reviewed journals.

"TX-001HR is the first bio-identical combination hormone therapy of estradiol in combination with progesterone to be evaluated in a large, well-controlled, randomized clinical trial," said TherapeuticsMD Chief Medical Officer Sebastian Mirkin, M.D. "The Replenish Trial demonstrated for the first-time safety and robust efficacy for the treatment of hot flashes at multiple doses of TX-001HR. If approved, TX-001HR estradiol 1 mg/progesterone 100 mg and TX-001HR estradiol 0.5 mg/progesterone 100 mg would provide TherapeuticsMD with a complete portfolio to meet the demands of women currently taking unapproved compounded hormones for the treatment of VMS, along with the healthcare providers and pharmacies that prescribe and compound these products."

About TX-001HR

TX-001HR is a novel combination of 17ß-estradiol and natural progesterone under investigation for treating vasomotor symptoms related to menopause. If approved by the FDA, TX-001HR would represent the first bio-identical estradiol and progesterone approved for use in a single, combined product for postmenopausal women with an intact uterus offering women an important alternative to both the available FDA-approved synthetic (non-bio-identical) hormones and the unapproved compounded bio-identical hormone products. Bio-identical refers to estradiol and progesterone that are molecularly identical to the hormones circulating naturally in the woman's body. An estimated one to two-and-a-half million women in the U.S. are using unapproved, compounded bio-identical hormone therapies to treat vasomotor symptoms.(2) Leading medical societies and the FDA advise that compounded hormone therapies may pose significant risk to women given lack of efficacy and safety data and lack of uniform manufacturing processes.

TX-001HR was developed using TherapeuticsMD's unique SYMBODA(TM) technology (meaning "similar to the body" , which enables partial and complete solubilization of estradiol and progesterone into medium-chain fatty acid oils often derived from coconut oil.

About Menopause and Vasomotor Symptoms (VMS)

Menopause is a natural life-stage transition for women with an average onset of 51 years. According to the United States Census Bureau, approximately 43 million women in the U.S. are of menopausal age (45-64 years).(3)

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December 05, 2016 16:05 ET (21:05 GMT)