Daré Bioscience, Inc. (NASDAQ: DARE), a leader in women’s health
innovation, and its collaborator Strategic Science &
Technologies, LLC (SST), a Cambridge, MA based novel topical drug
delivery company, today announced positive topline data from the
exploratory Phase 2b RESPOND study evaluating topical Sildenafil
Cream, 3.6% (Sildenafil Cream) as a treatment for female sexual
arousal disorder (FSAD). The exploratory study was designed to test
the sensitivity of several patient reported outcome (PRO) efficacy
endpoints and their ability to determine a treatment effect of
Sildenafil Cream compared to placebo to inform the ongoing
development of Sildenafil Cream. The study also served as a
validation study of exploratory endpoints that could be candidate
endpoints in a Phase 3 study of Sildenafil Cream. Although the
exploratory study was underpowered to assess statistical
significance, certain endpoints achieved statistical significance.
FSAD is the inability to reach or maintain a sufficient physical
response to sexual stimulation and, of the various types of female
sexual dysfunction disorders, FSAD is most analogous to erectile
dysfunction (ED) in men. Sildenafil, a phosphodiesterase-5 (PDE-5)
inhibitor, is the active ingredient in a tablet for oral
administration currently marketed under the brand name Viagra® for
the treatment of ED in men. Sildenafil Cream is an investigational
proprietary topical cream formulation of sildenafil specifically
designed to increase blood flow to the genital tissue in women. If
development is successful, Sildenafil Cream has the potential to be
the first FDA-approved treatment for FSAD. Market research suggests
that 16% of women in the U.S. ages 21 to 60, or approximately 10
million women, are distressed from experiencing symptoms associated
with FSAD, including lack of or low sexual arousal, and are
actively seeking solutions to improve their condition. In
comparison, the prevalence of complete ED in men is estimated to be
about 5% of men at age 40, increasing to about 15% at age 70.
“We are very pleased with the topline data from the Phase 2b
RESPOND study. Although the study was underpowered to assess
statistical significance, we saw statistically significant results
for certain of the endpoints, and the data indicate that, as
compared to placebo, Sildenafil Cream had a therapeutic effect
based on several PROs,” said Sabrina Martucci Johnson, President
and CEO of Daré Bioscience. “Because there are currently no
FDA-approved treatments for FSAD, there are no efficacy endpoints
that have been previously approved for use in a Phase 3 pivotal
study for potential treatment for FSAD – but with the data from the
Phase 2b RESPOND study we believe certain of the primary,
secondary, and exploratory endpoints could be candidate endpoints
in a Phase 3 study of Sildenafil Cream. Having now completed this
pioneering work in the field of FSAD, we look forward to reviewing
the data with the FDA, including discussing the data from
assessments as early as the 4- and 8-week mark after randomization,
and continuing the development of Sildenafil Cream, including our
objective of initiating the first ever Phase 3 pivotal study for
the treatment of FSAD. Following clinical development, Daré intends
to leverage the existing safety and efficacy data on the active
ingredient in Sildenafil Cream to utilize the FDA’s 505(b)(2)
pathway to obtain marketing approval of Sildenafil Cream in the
U.S.”
"The FDA has not approved any pharmacologic options for FSAD, a
condition which significantly compromises a woman's ability to have
a pleasurable sexual experience," commented Dr. Sheryl
Kingsberg, Division Chief of Behavioral Medicine, Department
of OBGYN, University Hospitals Cleveland Medical Center, Ohio, and
Past President of The International Society for the Study of
Women's Sexual Health, as well as co-editor of the Textbook of
Female Sexual Function and Dysfunction: Diagnosis and Treatment.
"Based on the topline data from the Phase 2b RESPOND study I am
very excited about the potential for this topical Sildenafil Cream
to address this critical unmet need in women's sexual health.
Leveraging the known therapeutic benefit of the active ingredient
in Viagra®, sildenafil, in a cream formulation to stimulate
increased blood flow to the genital tissue, Sildenafil Cream may
offer women a safe, effective and ‘on demand' solution to
difficulties with sexual arousal allowing for a more intense and
enjoyable sexual experience."
Unlike the oral formulations of PDE-5 inhibitors, Sildenafil
Cream is designed to be applied locally to the vulvar-vaginal
tissue prior to sexual activity to facilitate vasodilation and
increase blood flow directly to the genital tissue to improve the
physical arousal response to address the lack of those genital
arousal sensations commonly associated with FSAD. Increasing blood
flow to the genital tissue, as Sildenafil Cream is designed to do,
has the potential to improve genital arousal response and overall
sexual experience for women. This is similar to the way ED
medications work in men by directing blood flow to the genitals
when taken prior to sexual activity.
“The topline data from the Phase 2b RESPOND study represent an
important milestone in the field of female sexual dysfunction,”
said Dr. Andrew Goldstein, Medical Advisor of Daré Bioscience and
Past President of The International Society for the Study of
Women's Sexual Health, as well as co-editor of the Textbook of
Female Sexual Function and Dysfunction: Diagnosis and Treatment.
“It is exciting to be working at the cutting edge of research
focused on women’s sexual health and to advance a potential
first-in-category treatment option for women suffering with
FSAD.”
“It is encouraging to see sponsors such as Daré and SST
developing endpoints that will foster approval of new medicines for
women in FSAD. The previously completed content validation study
and the exit interviews completed as part of the Phase 2b RESPOND
study are significant steps to gaining regulatory approval of
endpoints in this area. I look forward to continuing our
collaboration by using the Phase 2b RESPOND study data to conduct
psychometric analyses to further refine the measures and resulting
endpoints for use in a Phase 3 pivotal study,” said Tara Symonds,
Ph.D., Managing Director, UK, and Chief Scientific Officer at
Clinical Outcomes Solutions, who is an advisor to Daré and SST and
has extensive expertise in the development and validation of PROs
for sexual health clinical trials, including establishing and
leading Pfizer’s PRO Center of Excellence earlier in her
career.
Daré plans to submit data from the Phase 2b RESPOND clinical
study of Sildenafil Cream for publication in a peer-reviewed
journal.
About the Exploratory Phase 2b RESPOND
Study
Study Design
The exploratory Phase 2b RESPOND study was a multi-center,
double-blind, randomized, placebo-controlled study to evaluate the
efficacy and safety of Sildenafil Cream in premenopausal patients
with FSAD. The study was a first of its kind Phase 2b clinical
study that includes PRO instruments to screen eligible women with
FSAD and included two co-primary endpoints, a secondary endpoint,
and a number of exploratory endpoints to measure, among other
things, improvement in localized genital sensations of arousal,
reduction in the distress that women experience with FSAD and
satisfactory sexual events. There are no FDA-approved treatments
for FSAD and thus there are no efficacy endpoints that have been
previously validated in a Phase 3 pivotal study for potential
treatments for FSAD.
The FDA requested that any PROs for use in the assessment of
efficacy in a Phase 3 study be adequately validated. Part of that
validation of the PROs includes exit interviews performed as part
of the Phase 2b RESPOND study to better understand qualitatively
what constitutes a meaningful change to the subjects. These
qualitative assessments of meaningful change were utilized to
determine which endpoints achieved meaningful improvement in the
Sildenafil Cream group. Additional psychometric analyses using the
Phase 2b RESPOND study dataset is planned to further refine and
validate the measures to inform the most appropriate endpoints for
use in a Phase 3 pivotal study.
The Phase 2b RESPOND study began with 99 subjects in the
Sildenafil Cream intent to treat population and 93 subjects in the
placebo intent to treat population, with 70 subjects in the
Sildenafil Cream intent to treat population and 60 subjects in the
placebo intent to treat population completing the study, and
therefore was underpowered to assess statistical significance.
During the study, participants used Sildenafil Cream and a placebo
cream in their home setting and documented their experience using
PRO instruments. The study evaluated Sildenafil Cream compared to
placebo cream over 12 weeks of dosing following both a non-drug and
placebo run-in period.
Study Efficacy Results and Safety
Summary of Topline DataA co-primary endpoint of the Phase 2b
RESPOND study was to evaluate the efficacy of Sildenafil Cream
compared to placebo as measured by change from baseline to the end
of the study in the Arousal-Sensation Domain of the 28-item Sexual
Function Questionnaire (SFQ28). The endpoint did not achieve
statistical significance. However, the change at the end of the
study in the group treated with Sildenafil Cream was consistent
with how women reported meaningful improvement in an exit interview
at the end of the study.
The other co-primary endpoint was to evaluate the efficacy of
Sildenafil Cream compared to placebo as measured by change from
baseline to the end of the study in the score for feeling concerned
by difficulties with sexual arousal. The change was assessed using
the previously validated Female Sexual Distress Scale – Desire,
Arousal and Orgasm (FSDS-DAO) Survey. This assessment did not
differentiate Sildenafil Cream from placebo.
The secondary endpoint of the study was to evaluate the efficacy
of Sildenafil Cream compared to placebo as measured by change from
baseline to the end of the study in the number of satisfactory
sexual events based on the subjects’ response to a question
answered and recorded via electronic diary within 24 hours after
each sexual event. The endpoint was selected because it can serve
as a primary endpoint in a Phase 3 study based on the FDA draft
2016 guidance document for female sexual dysfunction. When measured
at the 4- and 8-week mark after randomization, subjects treated
with Sildenafil Cream had a higher proportion of satisfying sexual
events during the prior month (68.6% and 74.1% at the 4- and 8-week
mark, respectively) compared to those treated with placebo (47.9%
and 67.9% at the 4- and 8-week mark, respectively) (week 4 P value
= 0.04).
The exploratory endpoints (selected based on the Content
Validity study conducted by SST and Daré) included endpoints
related to genital arousal, genital blood flow, lubrication,
orgasm, concerns about difficulties with sexual arousal, and other
assessments including questions regarding satisfying sexual events.
The exploratory endpoints were assessed at multiple periods over
the course of the study via electronic diary.
- An exploratory endpoint regarding
concerns about difficulties with sexual arousal differentiated
Sildenafil Cream versus placebo. Specifically, when asked about
their overall impression of change regarding their concerns about
difficulties with sexual arousal, women treated with Sildenafil
Cream were more likely to report an overall improvement. Based on
responses to the question at the 4-, 8- and 12-week mark after
randomization, 44% to 49% of the subjects treated with Sildenafil
Cream reported an overall improvement compared to 37% to 44% of the
subjects treated with placebo (P value < 0.01).
- Exploratory endpoints related to
arousal lubrication and achievement and pleasure of orgasm also
demonstrated important differences between the subjects treated
with Sildenafil Cream compared to placebo as measured by change
from baseline to the 8-week mark after randomization, at P value =
0.059 and P value = 0.066, respectively (trending toward
significance despite the small number of subjects in each group,
n=73 in the Sildenafil Cream intent to treat group and n=64 in the
placebo intent to treat group for these assessments).
- 48.7% of the
subjects treated with Sildenafil Cream reported an increase in
their overall satisfaction with sexual activity measured at the end
of the study, compared to 42.6% of the subjects treated with
placebo.
Summary of Cited Top Line DataThe exploratory Phase 2b RESPOND
study was underpowered to assess statistical significance, although
statistical significance was achieved on certain assessments. The
following table sets forth certain data regarding the co-primary
endpoints, the secondary endpoint, and certain exploratory
endpoints:
Objective/Endpoint |
|
Measured At |
Sildenafil Cream, N(1) |
Placebo, N(1) |
P
value |
Co-Primary: SFQ28 Arousal
Sensation Domain |
|
End of study (week 12) |
70 |
60 |
>0.05 |
Co-Primary: FSDS-DAO Survey (Q14
only (Concerned by difficulties with sexual arousal)) |
|
End of study (week 12) |
70 |
60 |
>0.05 |
Secondary: Proportion
of Satisfactory Sexual Events per Month during Double Blind
Treatment Period |
|
Week 4 |
78 |
68 |
0.04 |
|
Week 8 |
73 |
64 |
>0.05 |
|
Week 12 |
71 |
61 |
>0.05 |
Exploratory: Arousal Lubrication
PROs |
|
Week 8 |
73 |
64 |
0.059 |
Exploratory: Orgasm PROs |
|
Week 8 |
73 |
64 |
0.066 |
Exploratory: Regarding Concern
for FSAD Symptoms(2) |
|
Weeks 4 - 12 |
78 |
68 |
<0.01 |
Exploratory: Regarding
Satisfactory Sexual Activity(2) |
|
Weeks 4 - 12 |
78 |
68 |
<0.01 |
(1) The numbers in
this column represent the number of subjects included in the
assessment at the indicated time point. |
(2) This exploratory
endpoint was measured periodically beginning at week 4 after
randomization through the end of the study. |
SafetySildenafil Cream was generally safe and well-tolerated.
There were no treatment related serious adverse events and the
majority of treatment related adverse events were mild in
severity.
About FSAD and Sildenafil Cream, 3.6%
FSAD is distinct from hypoactive sexual desire disorder (HSDD)
in women, which is characterized primarily by a lack of sexual
desire. FSAD is a condition characterized primarily by a persistent
or recurrent inability to attain or maintain sufficient genital
arousal (an adequate lubrication-swelling response) during sexual
activity, frequently resulting in distress or interpersonal
difficulty. As with ED in men, FSAD is associated with insufficient
blood flow to the genitalia.
Market research suggests that 16% of women in the U.S. ages 21
to 60, or approximately 10 million women, are distressed from
experiencing symptoms associated with FSAD, including lack of or
low sexual arousal, and are actively seeking solutions to improve
their condition. In comparison, the prevalence of complete ED in
men is estimated to be about 5% of men at age 40, increasing to
about 15% at age 70. Daré believes the potential market opportunity
for an FDA-approved treatment for FSAD is comparable in size to the
market for FDA-approved treatments for ED in men.
Sildenafil Cream, 3.6% is an investigational proprietary cream
formulation of sildenafil, a PDE-5 inhibitor, designed for topical
administration to the vulvar-vaginal tissue to increase genital
blood flow and provide improvements in the female genital arousal
response, while avoiding systemic side effects observed with oral
formulations of sildenafil. Sildenafil Cream has been previously
evaluated in Phase 1 and Phase 2a clinical studies. In a Phase 1
clinical study in 20 healthy post-menopausal women, topical
Sildenafil Cream was safe and well tolerated at clinically relevant
doses, and study subjects reported favorable product
characteristics: easy to use and readily absorbed. In a Phase 2a
study in women with FSAD (15 pre-menopausal and 16
post-menopausal), Sildenafil Cream increased measurable blood flow
to the genital tissue compared to placebo cream. Further, data from
a thermography study in six healthy women demonstrated
significantly greater increases in genital temperature after
administration of Sildenafil Cream compared to placebo cream,
indicating a positive impact on genital blood flow during the
30-minute testing session, with statistical separation from placebo
within the first 15 minutes of dosing.
About Daré Bioscience
Daré Bioscience is a biopharmaceutical company committed to
advancing innovative products for women’s health. The company’s
mission is to identify, develop and bring to market a diverse
portfolio of differentiated therapies that prioritize women's
health and well-being, expand treatment options, and improve
outcomes, primarily in the areas of contraception, vaginal health,
reproductive health, menopause, sexual health and fertility.
Daré’s first FDA-approved product, XACIATO™ (clindamycin
phosphate) vaginal gel, 2% is a lincosamide antibacterial indicated
for the treatment of bacterial vaginosis in female patients 12
years of age and older, which is under a global license agreement
with Organon. XACIATO is a clear, colorless, viscous gel, to be
administered once intravaginally as a single dose. Daré’s portfolio
also includes potential first-in-category candidates in clinical
development: Ovaprene®, a novel, hormone-free monthly intravaginal
contraceptive whose U.S. commercial rights are under a license
agreement with Bayer; Sildenafil Cream, 3.6%, a novel cream
formulation of sildenafil to treat female sexual arousal disorder
utilizing the active ingredient in Viagra®; and DARE-HRT1, a
combination bio-identical estradiol and progesterone intravaginal
ring for menopausal hormone therapy. To learn more about XACIATO,
Daré’s full portfolio of women’s health product candidates, and
Daré’s mission to deliver differentiated therapies for women,
please visit www.darebioscience.com.
Daré may announce material information about its finances,
product and product candidates, clinical trials and other matters
using the Investors section of its website
(http://ir.darebioscience.com), SEC filings, press releases, public
conference calls and webcasts. Daré will use these channels to
distribute material information about the company, and may also use
social media to communicate important information about the
company, its finances, product and product candidates, clinical
trials and other matters. The information Daré posts on its
investor relations website or through social media channels may be
deemed to be material information. Daré encourages investors, the
media, and others interested in the company to review the
information Daré posts in the Investors section of its website and
to follow these Twitter accounts: @SabrinaDareCEO and
@DareBioscience. Any updates to the list of social media channels
the company may use to communicate information will be posted in
the Investors section of Daré’s website.
Forward-Looking Statements
Daré cautions you that all statements, other than statements of
historical facts, contained in this press release, are
forward-looking statements. Forward-looking statements, in some
cases, can be identified by terms such as “believe,” “may,” “will,”
“estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,”
“could,” “plan,” “potential,” “predict,” “seek,” “should,” “would,”
“contemplate,” “project,” “target,” “objective,” or the negative
version of these words and similar expressions. In this press
release, forward-looking statements include, but are not limited
to, statements relating to Sildenafil Cream’s potential as a safe
and effective therapy for FSAD, Daré’s plans for continued clinical
development of Sildenafil Cream, the anticipated regulatory pathway
for Sildenafil Cream, the potential for Sildenafil Cream to be the
first FDA-approved treatment for FSAD, and the potential market
opportunity for Sildenafil Cream. Forward-looking statements
involve known and unknown risks, uncertainties and other factors
that may cause Daré’s actual results, performance or achievements
to be materially different from future results, performance or
achievements expressed or implied by the forward-looking statements
in this press release, including, without limitation, risk and
uncertainties related to: the risk that topline results from a
clinical trial, including the Phase 2b RESPOND study, are based on
Daré’s preliminary analysis of key efficacy and safety data and,
following a comprehensive review of the study data, topline results
may not accurately reflect the complete results from the study and
the differences between topline results and complete results may be
significant and may adversely impact the continued clinical
development of the investigational product, including anticipated
time and expense of continued development; the risk that data from
the Phase 2b RESPOND study, which assessed multiple patient
reported outcomes at 4, 8 and 12 weeks after randomization, may not
be predictive of results of any future clinical study that assesses
safety and efficacy of Sildenafil Cream at time points beyond 12
weeks after randomization, and the double-blind dosing period the
FDA may require for a pivotal Phase 3 study of Sildenafil Cream is
unknown at this time; the risk that the FDA, other regulatory
authorities, members of the scientific or medical communities or
investors may not accept or agree with Daré’s interpretation of or
conclusions regarding the study data; Daré’s ability to raise
additional capital when and as needed to advance its product
candidates, execute its business strategy and continue as a going
concern; the risk that positive findings in early clinical and/or
nonclinical studies of a product candidate may not be predictive of
success in subsequent clinical and/or nonclinical studies of that
candidate; the risk that development of a product candidate
requires more clinical or nonclinical studies than Daré
anticipates; Daré’s ability to develop, obtain FDA or foreign
regulatory approval for, and commercialize its product candidates
and to do so on communicated timelines; failure or delay in
starting, conducting and completing clinical trials of a product
candidate; Daré’s ability to design and conduct successful clinical
trials, to enroll a sufficient number of patients, to meet
established clinical endpoints, to avoid undesirable side effects
and other safety concerns, and to demonstrate sufficient safety and
efficacy of its product candidates; Daré’s dependence on third
parties to conduct clinical trials and manufacture and supply
clinical trial material and commercial product; the loss of, or
inability to attract, key personnel; the effects of the COVID-19
pandemic, macroeconomic conditions and geopolitical events on
Daré’s operations, financial results and condition, and ability to
achieve current plans and objectives, including the potential
impact of the pandemic on Daré’s ability to timely commence,
enroll, conduct and report results of its clinical trials and on
the ability of third parties on which Daré relies to assist in the
conduct of its business to fulfill their contractual obligations to
Daré; the impact of pharmaceutical industry regulation and health
care legislation in the United States and internationally; the risk
that developments by competitors make Daré’s product or product
candidates less competitive or obsolete; difficulties establishing
and sustaining relationships with development and/or commercial
collaborators; failure of Daré’s product or product candidates, if
approved, to gain market acceptance or obtain adequate coverage or
reimbursement from third-party payers; Daré’s ability to retain its
licensed rights to develop and commercialize a product or product
candidate; Daré’s ability to satisfy the monetary obligations and
other requirements in connection with its exclusive, in-license
agreements covering the critical patents and related intellectual
property related to its product and product candidates; Daré’s
ability to adequately protect or enforce its, or its licensor’s,
intellectual property rights; the lack of patent protection for the
active ingredients in certain of Daré’s product candidates which
could expose its products to competition from other formulations
using the same active ingredients; product liability claims;
governmental investigations or actions relating to Daré’s product
or product candidates or the business activities of Daré, its
commercial collaborators or other third parties on which Daré
relies; the impact of pharmaceutical industry regulation and health
care legislation in the United States and internationally; global
trends toward health care cost containment; cyber attacks, security
breaches or similar events that compromise Daré’s technology
systems or those of third parties on which it relies and/or
significantly disrupt Daré’s business; and disputes or other
developments concerning Daré’s intellectual property rights. Daré’s
forward-looking statements are based upon its current expectations
and involve assumptions that may never materialize or may prove to
be incorrect. All forward-looking statements are expressly
qualified in their entirety by these cautionary statements. For a
detailed description of Daré’s risks and uncertainties, you are
encouraged to review its documents filed with the SEC including
Daré’s recent filings on Form 8-K, Form 10-K and Form 10-Q. You are
cautioned not to place undue reliance on forward-looking
statements, which speak only as of the date on which they were
made. Daré undertakes no obligation to update such statements to
reflect events that occur or circumstances that exist after the
date on which they were made, except as required by law.
Contacts:
Investors on behalf of Daré Bioscience, Inc.:Lee RothBurns
McClellanlroth@burnsmc.com646.930.4406
OR
Media on behalf of Daré Bioscience, Inc.:Jake RobisonEvoke
Canalejake.robison@evokegroup.com619.849.5383
Source: Daré Bioscience, Inc.
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