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

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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)–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.


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
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 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 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 United States Census Bureau,
approximately 43 million women in the U.S. are of menopausal age (45-64
years).3

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.

Conference Call and Webcast

TherapeuticsMD will host a conference call today, during which
management will discuss the top-line results of the pivotal phase 3
Replenish Trial. Details for the call are:

Date: December 5, 2016

Time: 4:30 p.m. ET

Telephone Access (US): (866) 665-9531

Telephone Access (International): (724) 987-6977

Access Code for All Callers: 30215405

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 TherapeuticsMD, Inc.

TherapeuticsMD, Inc. is an innovative healthcare company focused on
developing and commercializing products exclusively for women. With its
SYMBODA technology, TherapeuticsMD is developing advanced
hormone therapy pharmaceutical products to enable delivery of
bio-identical hormones through a variety of dosage forms and
administration routes. The company’s clinical development pipeline
includes two phase 3 products. The company also manufactures and
distributes branded and generic prescription prenatal vitamins under the
vitaMedMD® and BocaGreenMD® brands. More
information is available at the following websites: www.therapeuticsmd.com,
www.vitamedmd.com
and www.bocagreenmd.com.

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 FDA will accept and approve the application;
whether the FDA will approve the company’s new drug application for its
TX-004HR product candidate and whether any such approval will occur by
the PDUFA date; the length, cost and uncertain results of the company’s
clinical trials; the potential of adverse side effects or other safety
risks that could preclude the approval of the company’s hormone therapy
drug candidates; the company’s reliance on third parties to conduct its
clinical trials, research and development and manufacturing; the
availability of reimbursement from government authorities and health
insurance companies for the company’s products; the impact of product
liability lawsuits; the influence of extensive and costly government
regulation; the volatility of the trading price of the company’s common
stock and the concentration of power in its stock ownership. PDF copies
of the company’s historical press releases and financial tables can be
viewed and downloaded at its website:
www.therapeuticsmd.com/pressreleases.aspx.

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 United States Census Bureau

Contacts

TherapeuticsMD, Inc.
Investor Contact
David
DeLucia, 561-961-1900
Director, Investor Relations
David.DeLucia@TherapeuticsMD.com
or
Media
Contact

SparkBioComm
Ami Knoefler, 650-739-9952
Ami@SparkBioComm.com