Significant Reduction in Dehydroepiandrosterone
Sulfate (DHEAS) Versus Placebo Observed in Women with Elevated
DHEAS Levels at Baseline
Increase in Serum Sex Hormone Binding Globulin
(SHBG) Versus Placebo Observed
Tildacerfont was Well-Tolerated with No Safety
Signals
Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage
biopharmaceutical company focused on developing and commercializing
novel therapies for endocrine disorders with significant unmet
medical need, presented results from its Phase 2 POWER study of
tildacerfont, a second-generation CRF1 receptor antagonist, for the
treatment of polycystic ovary syndrome (PCOS) at the 2024 Annual
Meeting of the Endocrine Society (ENDO 2024).
“There is a significant unmet medical need for new PCOS
treatments as there are currently no FDA-approved therapies, and
the standard of care only addresses symptoms,” said Lubna Pal,
MBBS, FACOG, M.S., Director, Program for Polycystic Ovary Syndrome,
Yale Reproductive Endocrinology, Department of Obstetrics,
Gynecology and Reproductive Sciences, Yale University School of
Medicine. “The results of this study are exciting; by demonstrating
the ability of tildacerfont to reduce DHEAS, it is plausible that a
myriad of health risks that are consequent to chronic
hyperandrogenism could be harnessed with this approach.”
Will Charlton, M.D., M.A.S., Chief Medical Officer, Spruce
Biosciences, commented, “We are grateful to our partners, study
investigators, and patients who contributed to the POWER study,
which brings us one step closer to more effective treatments for
PCOS, a highly prevalent condition with significant unmet medical
need. Further studies of tildacerfont for the treatment of PCOS are
warranted, and we continue to evaluate strategic collaboration
opportunities to advance this potentially disease-modifying
treatment option forward.”
Phase 2 POWER Study
Results
The POWER study enrolled 27 women with a confirmed diagnosis of
PCOS. Participant demographics and baseline hormone levels are
detailed in Table 1 below.
Table 1. Summary of Demographics and Baseline Hormones; Intent
to Treat Analysis Population
Key Variables
Mean (SD)
Tildacerfont
(n = 17)
Placebo
(n = 10)
Total
(n = 27)
Age
28.4 (5.6)
29.3 (5.5)
28.7 (5.4)
Age at PCOS Diagnosis
22.6 (6.3)
21.6 (6.0)
22.3 (6.1)
BMI (kg/m2)
32.1 (5.8)
32.4 (12.5)
32.2 (8.6)
DHEAS (µg/dL)
351.3 (90.5)
387.8 (107.2)
364.8 (96.7)
17-OHP (ng/dL)
83.2 (86.3)
62.1 (54.1)
75.4 (75.5)
ACTH (pg/mL)
23.9 (11.9)
22.3 (12.0)
23.3 (11.7)
A4 (ng/dL)
185.2 (75.2)
130.0 (66.0)
166.8 (75.6)
T (ng/dL)
61.0 (22.0)
61.1 (27.0)
61.0 (23.4)
Screening DHEAS > ULN, N (%)
Yes
No
12 (70.6%)
5 (29.4%)
7 (70.6%)
3 (29.4%)
19 (70.4%)
8 (29.6%)
In women with elevated baseline DHEAS, a significant reduction
in DHEAS versus placebo was observed (p = 0.020).
Table 2. Change from Baseline in DHEAS (μg/dL) at Week 12;
Modified Intent to Treat Analysis; Baseline DHEAS > Upper Limit
of Normal (ULN)
Tildacerfont
(n = 12) 1
Placebo
(n = 7) 1
n
112
53
Mixed Model of Repeated
Measures
Least Squares (LS) Geometric Mean Ratio (%
Change from Baseline)
0.876 (-12.4%)
1.057 (5.7%)
95% Confidence Interval (CI) of Geometric
Mean Ratio
0.802, 0.955
0.931, 1.200
95% CI of Percent Change from Baseline
-19.8%, -4.5%
-6.9%, 20.0%
Difference LS Mean Ratio
[tildacerfont/placebo]
0.828
N/A
95% CI of Difference LS Mean Ratio
0.709, 0.967
N/A
p-value
0.020
N/A
- Eight subjects (five in the tildacerfont arm and three in the
placebo arm) did not meet inclusion criteria #3 requiring DHEAS to
be greater than the ULN and were excluded from the analyses.
- One subject was excluded from the analyses due to no
post-baseline DHEAS assessment.
- Two subjects were excluded from the analyses due to concomitant
glucocorticoid (GC) use, which confounded assessment of adrenal
steroid reduction.
In study participants, a significant increase in SHBG versus
placebo was observed (p = 0.012).
Table 3. Change from Baseline in SHBG (nmol/L) at Week 12;
Modified Intent to Treat Analysis
Tildacerfont
(n = 17)
Placebo
(n = 10)
n
161
91
Mixed Model of Repeated
Measures
LS Geometric Mean Ratio (% Change from
Baseline)
1.329 (32.9%)
0.919 (-8.1%)
95% CI of Geometric Mean Ratio
1.124, 1.571
0.735, 1.148
95% CI of Percent Change from Baseline
12.4%, 57.1%
-26.5%, 14.8%
Difference LS Mean Ratio
[tildacerfont/placebo]
1.446
N/A
95% CI of Difference LS Mean Ratio
1.093, 1.913
N/A
p-value
0.012
N/A
- Two subjects (one in the tildacerfont arm and one in placebo
arm) did not have a week 12 SHBG assessment completed.
The Phase 2 study was not powered to test for statistical
significance on the primary endpoint. However, the lowering of
DHEAS, an adrenal androgen precursor, observed with 12-week
exposure, suggests that tildacerfont may be of therapeutic benefit
for some women with PCOS. Additionally, the observed increase in
SHBG may potentially result in lower levels of free, bioactive sex
hormones such as testosterone.
Tildacerfont was well-tolerated with no safety signals observed.
The majority of adverse events were mild to moderate. No serious
adverse reactions were reported.
About POWER Study
The POWER study was a Phase 2 proof-of-concept, randomized,
placebo-controlled dose escalation study which evaluated the safety
and efficacy of tildacerfont titrated to 200 mg QD compared to
placebo at 12 weeks of treatment in 27 female subjects with
polycystic ovary syndrome (PCOS) and adrenal androgens as measured
by dehydroepiandrosterone sulfate (DHEAS) levels at baseline. The
primary endpoint of this clinical trial was the absolute change
from baseline in DHEAS. Additional secondary endpoints included
safety and tolerability, the proportion of subjects who achieve a
30% or greater reduction in DHEAS and change from baseline in
hormonal biomarkers.
About Tildacerfont
Tildacerfont is a potent and highly selective, non-steroidal,
oral antagonist of the CRF1 receptor, which is the receptor for
corticotropin-releasing factor (CRF), a hormone that is secreted by
the hypothalamus. The CRF1 receptor is abundantly expressed in the
pituitary gland where it is the primary regulator of the
hypothalamic–pituitary-adrenal (HPA) axis. By blocking the CRF1
receptor, tildacerfont has the potential to reduce the production
of adrenocorticotropic hormone (ACTH) in the pituitary gland and
limit the amount of androgens produced downstream from the adrenal
gland. Adrenal androgen excess in PCOS appears to result from an
elevation of, or hypersensitivity to, ACTH. Tildacerfont may
provide a therapeutic option to treat the underlying cause of
disease through reductions of ACTH, which may improve clinical
symptoms of PCOS, such as hair growth, acne, irregular periods and
infertility. No drug-related serious adverse events have been
reported related to tildacerfont treatment in completed
studies.
About Polycystic Ovary Syndrome (PCOS)
Polycystic ovary syndrome, or PCOS, is a hormonal disorder
common among females of reproductive age affecting nearly five
million females in the United States and approximately 115 million
females worldwide. PCOS is characterized by elevated levels of
androgens, cysts in the ovaries and irregular periods. Females with
PCOS present with additional symptoms, including hirsutism,
alopecia, acne, infertility, weight gain, fatigue, depression and
mood changes. The underlying causes of PCOS are unknown. However,
excess insulin secretion and low-grade inflammation, which
stimulate the polycystic ovaries, have been linked to androgen
excess. The source of this androgen excess may be ovarian, adrenal,
both adrenal and ovarian, or from other sources. Adrenal androgen
excess in PCOS may occur independently of ovarian androgen excess,
suggesting it may represent an intrinsic and possible primary
source of abnormal synthesis of androgens. Adrenal androgen excess
in PCOS does not result from enzymatic deficiencies, but rather
from an altered adrenal responsivity to ACTH.
About Spruce Biosciences
Spruce Biosciences is a late-stage biopharmaceutical company
focused on developing and commercializing novel therapies for
endocrine disorders with significant unmet medical need. Spruce is
developing tildacerfont, a second-generation CRF1 receptor
antagonist, for patients suffering from classic congenital adrenal
hyperplasia (CAH) and polycystic ovary syndrome (PCOS). To learn
more, visit www.sprucebio.com and follow us on X @Spruce_Bio,
LinkedIn, Facebook and YouTube.
Forward-Looking Statements
Statements contained in this press release regarding matters
that are not historical facts are “forward-looking statements”
within the meaning of the Private Securities Litigation Reform Act
of 1995. Such forward-looking statements include statements
regarding, among other things, the design, results, conduct,
progress and timing of Spruce’s clinical trials; the potential of
tildacerfont to reduce DHEAS for the treatment of PCOS; the
potential of tildacerfont to increase SHBG and lower free bioactive
sex hormones; and Spruce’s product candidate, strategy and
regulatory matters. Because such statements are subject to risks
and uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Words such
as “potential”, “suggest” and similar expressions are intended to
identify forward-looking statements. These forward-looking
statements are based upon Spruce’s current expectations and involve
assumptions that may never materialize or may prove to be
incorrect. Actual results could differ materially from those
anticipated in such forward-looking statements as a result of
various risks and uncertainties, which include, without limitation,
risks and uncertainties associated with Spruce’s business in
general, the impact of geopolitical and macroeconomic events, and
the other risks described in Spruce’s filings with the U.S.
Securities and Exchange Commission. All forward-looking statements
contained in this press release speak only as of the date on which
they were made and are based on management’s assumptions and
estimates as of such date. Spruce 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20240603519582/en/
Media Katie Beach Oltsik Inizio Evoke Comms (937)
232-4889 Katherine.Beach@inizioevoke.com media@sprucebio.com
Investors Samir Gharib President and CFO Spruce
Biosciences, Inc. investors@sprucebio.com
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