TherapeuticsMD Announces FDA Approval of ANNOVERA™ (Segesterone Acetate/Ethinyl Estradiol Vaginal System) for Birth Control

The first and only birth control approved as a vaginal system

The first and only patient-controlled, procedure-free, long-acting,
reversible prescription birth control product to provide a full year of
protection from pregnancy

TherapeuticsMD will host a conference call on Monday, August 13th
at 8:30 a.m. EDT

BOCA RATON, Fla.–(BUSINESS WIRE)–TherapeuticsMD, Inc. (NASDAQ:TXMD), an innovative women’s healthcare
company, today announced that the United States (U.S.) Food and Drug
Administration (FDA) has approved ANNOVERA™ (segesterone acetate/ethinyl
estradiol vaginal system), the first long-acting prescription birth
control that is patient-controlled, procedure-free and reversible. The
ANNOVERA contraceptive vaginal system is a small, soft flexible ring
that prevents ovulation for an entire year (13 cycles) and can be
inserted and removed by a woman at her discretion in repeated four-week
cycles (remaining in place continuously for three weeks followed by
removal for one week).

The segesterone acetate component of the ANNOVERA contraceptive vaginal
system is expected to be classified as a “new chemical entity,” or NCE,
by the FDA and thus will likely be entitled to five years of regulatory
exclusivity under the Drug Price Competition and Patent Term Restoration
Act of 1984, otherwise known as the Hatch-Waxman Act. This unique
contraceptive vaginal system technology combines low doses of a novel
progestin, Nestorone® (segesterone acetate), with a widely
used estrogen (ethinyl estradiol). The contraceptive vaginal system
works by releasing an average continuous daily dose of 0.15 mg/day of
segesterone acetate and 0.013 mg/day of ethinyl estradiol to prevent

“The U.S. contraceptive market is shifting toward long-acting solutions
and we believe ANNOVERA represents an exciting new entrant for women and
healthcare providers by providing the first woman-controlled,
procedure-free, long-acting, reversible birth control product putting
the woman in control of both her fertility and menstruation,” said Dr.
Brian Bernick, Co-Founder of TherapeuticsMD. “We believe ANNOVERA can
help meet the needs of women who are looking for long-acting solutions,
including women who have never given birth and women who are not in a
monogamous relationship, who are often counseled not to use many of the
currently available long-acting contraceptive products.”

ANNOVERA was developed by the global non-profit research organization,
Population Council, a leading developer of long-acting, reversible
contraceptives. The FDA approval of ANNOVERA is based in part on data
from 17 clinical trials, including safety and efficacy data from three
open-label trials that included 2,308 healthy women in total. The data
showed that ANNOVERA was 97.3% effective in preventing pregnancy when
used as directed – making it among the most effective women-controlled
methods of contraception. Based on pooled data from the two trials of
2,111 females ≤35 years of age, the primary endpoint Pearl Index (PI)
was 2.98 per 100 woman-years of ANNOVERA use. Results from the Phase 3
acceptability sub-study of 905 women support an overall satisfaction
rate of 89%, which was related to ease of use, side effects,
expulsions/feeling the product and effects during sexual activity. The
trials also demonstrated high rates of adherence and continuation for a
full year.1 The most common adverse reactions leading to
discontinuation by ≥ 1% of ANNOVERA-treated women included irregular
bleeding (metrorrhagia/menorrhagia) (1.7%), headache/migraine (1.3%),
vaginal discharge/vulvovaginal mycotic infections (1.3%), and
nausea/vomiting (1.2%). Consistent with other combination hormonal
contraceptives (CHCs), cigarette smoking increases the risk of serious
cardiovascular events from CHC use. Women over 35 years old who smoke
should not use ANNOVERA. Also consistent with other CHCs, women are at
increased risk for a venous thrombotic event (VTE) when using the
one-year contraceptive vaginal system. Limited data are available in
women with a Body Mass Index (BMI) greater than 29 kg/m2
because this population was excluded from the clinical trials after VTEs
were reported. A post-approval observational study will be performed to
measure the risk of venous thromboembolism. Important safety information
for ANNOVERA, including the boxed warning, is provided below.

“ANNOVERA’s approval and designation as a ‘vaginal system’ potentially
creates a new class of contraception that private health plans will be
required to cover with no patient out-of-pocket costs under the
Affordable Care Act (ACA),” said Robert Finizio, TherapeuticsMD CEO and
Co-Founder. “TherapeuticsMD intends to leverage its existing
infrastructure to commercialize ANNOVERA. Together with our prescription
menopausal hormone products and prenatal vitamins, TherapeuticsMD aims
to become the premier women’s healthcare company, offering a full
portfolio of products across the woman’s lifespan from contraception and
pregnancy through menopause.”

The U.S. market for prescription contraceptives generated more than $5
billion in net sales in 2017.2 An estimated 43 million women
in the U.S. are at risk of unintended pregnancy of which 18 million
women want to avoid pregnancy and nearly half of all pregnancies that
occur each year in the U.S. are unintended.3,4 According to
the National Center for Health and Statistics, use of long-acting
reversible contraceptives increased nearly 5-fold in the last decade
among women aged 15 to 44.5

TherapeuticsMD intends to leverage the Population Council’s existing
relationships with the supplier of segesterone acetate and the
manufacturer of the clinical trial supply of the one-year contraceptive
vaginal system to scale-up commercial manufacturing of ANNOVERA.
TherapeuticsMD currently estimates that ANNOVERA will be commercially
available as early as the third quarter of 2019 with the commercial
launch as early as the fourth quarter of 2019 or first quarter of 2020.
The ACA mandates that private health plans provide coverage with no
out-of-pocket costs for one treatment per class of in each of the
classes identified by the FDA for women in its Birth Control Guide. As
part of its license agreement with the Population Council,
TherapeuticsMD has agreed to provide significantly reduced pricing to
federally designated Title X family planning clinics serving
lower-income women.

Conference Call Information

TherapeuticsMD will host a conference call today to discuss the ANNOVERA
approval. Details for the call are:

Date:       Monday, August 13, 2018
Time: 8:30 a.m. EDT
Telephone Access (US): (866) 665-9531
Telephone Access (International): (724) 987-6977
Access Code for All Callers: 5239706

Additionally, a live webcast can be accessed on the company’s website,,
on the Home Page or under the “Investors & Media” section. A digital
recording of the conference call will be available for replay beginning
two hours after the call’s completion and for at least 30 days with the
dial-in (855) 859-2056 or international (404) 537-3406 and Conference
ID: 5239706.


The ANNOVERA one-year contraceptive vaginal system combines a widely
used estrogen (ethinyl estradiol) with a new progestin segesterone
acetate (Nestorone®) into a single ring to prevent ovulation
for an entire year (13 cycles; used in repeated four-week cycles
(remaining in place continuously for three weeks followed by removal for
one week)). Designed to empower women to be in complete control of their
fertility and menstruation, ANNOVERA represents the first and only
long-acting birth control product that is reversible and does not
require a medical procedure for insertion or removal. The soft, flexible
ring can be inserted and removed by the woman herself and without the
help of a healthcare professional. The one-year vaginal system
represents a new option for women, including nulliparous women (women
who have not given birth) desiring long-acting reversible contraception.
The one-year contraceptive vaginal system does not require refrigeration.


ANNOVERA is a progestin/estrogen CHC indicated for use by females of
reproductive potential to prevent pregnancy. (Limitation of use: Not
adequately evaluated in females with a BMI of > 29 kg/m2).

Important Safety Information

Cigarette smoking increases the risk of cardiovascular events from
CHC use. This risk increases with age, particularly in females over 35
years of age, and with the number of cigarettes smoked.
should not be used by females who are over 35 years of age and smoke.

Due to increased risks of serious side effects, ANNOVERA should not be
used in females with certain medical conditions, including females who
have a high risk of arterial or venous thrombotic diseases; who have or
have had breast cancer or other estrogen- or progestin-sensitive cancer;
who have liver tumors, acute hepatitis, severe cirrhosis, undiagnosed
abnormal uterine bleeding, or hypersensitivity to any ingredients in
ANNOVERA; who use certain Hepatitis C drug combinations; or who are
pregnant or breastfeeding.

Risks from use of a CHC, like ANNOVERA, particularly in females with any
condition listed above, include venous thrombotic events; cardiovascular
events and cerebrovascular events such as stroke and myocardial
infarction; liver disease; elevated liver enzymes with concomitant
Hepatitis C treatment; hypertension; carbohydrate and lipid metabolic
effects; headache; bleeding irregularities and amenorrhea.

ANNOVERA does not protect against HIV-infection (AIDS) and other
sexually transmitted infections.

Please note that this information is not comprehensive. Please see the
Full Prescribing Information, including the Boxed Warning, for ANNOVERA

About TherapeuticsMD, Inc.

TherapeuticsMD, Inc. is an innovative healthcare company focused on
developing and commercializing novel products exclusively for women. Our
products are designed to address the unique changes and challenges women
experience through the various stages of their lives with a therapeutic
focus in family planning/reproductive health and menopause management.
The company is committed to advancing the health of women and
championing awareness of their healthcare issues. To learn more about
TherapeuticsMD, please visit
or follow us on Twitter: @TherapeuticsMD and on Facebook: TherapeuticsMD.

About the Population Council

The Population Council ( confronts
critical health and development issues—from stopping the spread of HIV
to improving reproductive health and ensuring that young people lead
full and productive lives. Through biomedical, social science, and
public health research in 50 countries, the Council works with partners
to deliver solutions that lead to more effective policies, programs, and
technologies that improve lives around the world. Established in 1952
and headquartered in New York, the Council is a nongovernmental,
nonprofit organization governed by an international board of trustees.

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: whether
the FDA will approve the NDA for the company’s TX-001HR product
candidate and whether such approval will occur by the PDUFA target
action date; the company’s ability to maintain or increase sales of its
products; the company’s ability to develop and commercialize IMVEXXYTM,
ANNOVERA and its hormone therapy drug candidates and obtain additional
financing necessary therefor; whether the company will be able to comply
with the covenants and conditions under its term loan agreement; 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
or adversely affect the commercialization of the company’s current or
future approved products; 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:

1 Merkatz, RB, Plagianos M, Hoskin E, et al, Acceptability of
the nestorone®/ethinyl estradiol contraceptive vaginal ring: development
of a model; implications for introduction” Contraception. 2014
November; 90(5): 514–521.

2 IQVIA 2017, Company filings.

3 Guttmacher Institute, Fact Sheet: Contraceptive Use in the
United States, July 2018.

4 Finer LB and Zolna MR, Declines in unintended pregnancy in
the United States, 2008–2011, New England Journal of Medicine,
2016, 374(9):843–852,

5 Branum A and Jones J, Trends in Long-Acting Reversible
Contraception Use Among U.S. Women Aged 15-44, NCHS Data Brief, Number
188, February 2015.


TherapeuticsMD, Inc.
Investor Contact:
Nichol Ochsner,
561-961-1900, ext. 2088
Vice President Investor Relations