- 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
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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FDA ) draft guidance.1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
The results of the Replenish Trial (p-values of < 0.05 meet
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 | ||||||||||
Estradiol/Progesterone | 1 mg/100 mg | 0.5 mg/100 mg | 0.5 mg/50 mg | 0.25 mg/50 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(Ŧ) | ||||||||||
Endometrial Hyperplasia | 0% (0/280) | 0% (0/303) | 0% (0/306) | 0% (0/274) | 0% (0/92) | |||||
MITT = Modified intent to treat | ||||||||||
ŦPer FDA, consensus hyperplasia refers to the concurrence of two of the three pathologists be accepted as the final diagnosis1 |
||||||||||
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
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
“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
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
TX-001HR was developed using TherapeuticsMD’s unique SYMBODATM 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
As the ovaries stop producing hormones, levels of circulating estrogen decrease, often causing vasomotor symptoms (VMS) such as night sweats, hot flashes, and sleep disturbances. VMS affect as many as 60-80 percent of all menopausal women.
Menopausal women can benefit from hormone therapy (HT), also known as hormone replacement therapy (HRT), which is recognized by key medical societies as the most effective treatment for relief of symptoms related to menopause.
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Additionally, a live webcast of the conference call can be accessed on the company’s website, www.therapeuticsmd.com, under the “Investors & Media” section.
About
Forward Looking Statements
This press release by TherapeuticsMD, Inc. may contain
forward-looking statements. Forward-looking statements may include, but
are not limited to, statements relating to TherapeuticsMD’s objectives,
plans and strategies as well as statements, other than historical facts,
that address activities, events or developments that the company
intends, expects, projects, believes or anticipates will or may occur in
the future. These statements are often characterized by terminology such
as “believes,” “hopes,” “may,” “anticipates,” “should,” “intends,”
“plans,” “will,” “expects,” “estimates,” “projects,” “positioned,”
“strategy” and similar expressions and are based on assumptions and
assessments made in light of management’s experience and perception of
historical trends, current conditions, expected future developments and
other factors believed to be appropriate. Forward-looking statements in
this press release are made as of the date of this press release, and
the company undertakes no duty to update or revise any such statements,
whether as a result of new information, future events or otherwise.
Forward-looking statements are not guarantees of future performance and
are subject to risks and uncertainties, many of which are outside of the
company’s control. Important factors that could cause actual results,
developments and business decisions to differ materially from
forward-looking statements are described in the sections titled “Risk
Factors” in the company’s filings with the Securities and Exchange
Commission, including its most recent Annual Report on Form 10-K and
Quarterly Reports on Form 10-Q, as well as reports on Form 8-K, and
include the following: the company’s ability to maintain or increase
sales of its products; the company’s ability to develop and
commercialize its hormone therapy drug candidates and obtain additional
financing necessary therefor ; whether the company will be able to
prepare a new drug application for its TX-001HR product candidate and,
if prepared, whether the
References
1 2003 FDA Draft Guidance for Industry Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms – Recommendations for Clinical Evaluation http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm071643.pdf
2 Pinkerton JV, Santoro N. 2015. Menopause, Vol.22, No.9, pp 0-11
3
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Source:
TherapeuticsMD, Inc.
Investor Contact
David
DeLucia, 561-961-1900
Director, Investor Relations
David.DeLucia@TherapeuticsMD.com
or
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Contact
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