- CAHtalyst™ Pediatric Study Met Primary
Endpoint Demonstrating a Statistically Significant Decrease from
Baseline in Serum Androstenedione in Children and Adolescents with
Congenital Adrenal Hyperplasia
- Key Secondary Endpoint Demonstrated a Statistically
Significant Decrease from Baseline in Daily Glucocorticoid
Dose while Maintaining Androgen Control
- Crinecerfont Was Generally Well-Tolerated
- Company to Host Conference Call and Webcast Today at
8:00 a.m. ET with Management and Dr.
Richard Auchus, Professor of
Pharmacology and Internal Medicine, Division of Metabolism,
Endocrinology, and Diabetes at the University of
Michigan
SAN
DIEGO, Oct. 5, 2023 /PRNewswire/ -- Neurocrine
Biosciences, Inc. (Nasdaq: NBIX) today announced positive top-line
data from the Phase 3 CAHtalyst™ Pediatric Study evaluating the
efficacy, safety, and tolerability of crinecerfont in children and
adolescents with classic congenital adrenal hyperplasia (CAH) due
to 21-hydroxylase deficiency. Crinecerfont is an oral, selective
corticotropin-releasing factor type 1 receptor antagonist being
investigated to help reduce and control excess adrenal androgens
through a steroid-independent mechanism.
"The outstanding safety and efficacy results reported today for
the CAHtalyst Pediatric study and last month for the CAHtalyst
Adult study demonstrate the potential benefit of crinecerfont
across all groups studied, including children, adolescents and
adults," said Kevin Gorman, Ph.D.,
Chief Executive Officer, Neurocrine Biosciences, Inc.
"As a pediatric endocrinologist, I'm highly encouraged by the
results from the CAHtalyst Pediatric study and the potential of
crinecerfont to shift the treatment paradigm for a disorder that
has seen little innovation in many decades," said Kyriakie
Sarafoglou, M.D., Professor, Department of Pediatrics and
Department of Experimental and Clinical Pharmacology, Divisions of
Endocrinology and Genetics & Metabolism, University of Minnesota. "The data suggest
that crinecerfont might enable us to smooth out the numerous
adjustments we have to make in glucocorticoid doses to manage high
androgen levels as children grow, potentially improving clinical
outcomes related to androgen excess as well as chronic
supraphysiologic glucocorticoid dosing."
The Phase 3 Pediatric study met its primary endpoint,
demonstrating that treatment with crinecerfont resulted in a
statistically significant decrease in serum androstenedione from
baseline at Week 4 versus placebo following a glucocorticoid (GC)
stable period (p = 0.0002).
Importantly and consistent with the results from the Phase 3
CAHtalyst Adult study, crinecerfont treatment led to a
statistically significant percent reduction from baseline in daily
GC dose while maintaining androgen control at Week 28 versus
placebo (p < 0.0001). Approximately 30% of participants
receiving crinecerfont achieved a reduction to a physiologic GC
dose while maintaining androgen control compared to 0% of
participants receiving placebo. The study also met the other key
secondary endpoint demonstrating a statistically significant
decrease in serum 17-hydroxyprogesterone from baseline at Week 4
versus placebo (p < 0.0001).
Common Endpoints in
CAHtalyst™ Phase 3 Studies
|
P-value
|
Adult
n =
182
|
Pediatric
n =
103
|
Serum
Androstenedione – Change from baseline at Week 4
|
<0.0001
|
0.0002
|
GC Total Daily Dose
– Percent change from baseline at
Week 24 (Adult) / Week 28 (Pediatric), while maintaining
androgen control
|
<0.0001
|
<0.0001
|
Achieving Reduction
to Physiologic GC Dose – At Week 24
(Adult) / Week 28 (Pediatric), while maintaining
androgen control
|
<0.0001
|
0.0009*
|
*p-value not adjusted for
multiplicity
|
|
Crinecerfont was generally well tolerated. During the
double-blind, placebo-controlled period of the trial, the most
common adverse events were headache, fever, vomiting, upper
respiratory tract infection, and nasopharyngitis. There were
few serious adverse events, with none assessed as related to
crinecerfont.
There was a high rate of completion (>95%) in the 28-week
double-blind, placebo-controlled treatment period of the trial,
similar to the >95% completion rate observed in the
double-blind, placebo-controlled portion of the CAHtalyst Adult
study.
"The CAHtalyst studies represent the largest interventional
clinical trial program conducted in both pediatric and adult CAH
patients to date and enrolled a patient population that reflects
the unmet need in this condition, with both adult and pediatric
patients having inadequate androgen control at baseline despite
supraphysiologic glucocorticoid dosing," said Eiry W. Roberts,
M.D., Chief Medical Officer at Neurocrine Biosciences, Inc. "The
results from these studies suggest that crinecerfont could
represent a new standard of care for CAH patients with the ability
to reduce androgen levels through a non-glucocorticoid mechanism. I
am particularly excited about our positive results in the pediatric
patient population and what improved androgen control in the
setting of reduced glucocorticoid doses could mean for important
outcomes related to growth and development."
The data from the CAHtalyst Pediatric and Adult studies,
including data from the open-label treatment periods, will support
regulatory submissions to the FDA in 2024 and later to the European
Medicines Agency. Additional information regarding the results from
both Phase 3 CAHtalyst studies will be provided at the Company's
December 2023 Analyst Day and in a
peer-reviewed medical journal.
Conference Call and Webcast Today at 8:00 a.m. Eastern Time
The Company will
discuss the results, baseline characteristics and additional data
from the Phase 3 CAHtalyst Pediatric and CAHtalyst Adult studies on
a Conference Call at 8:00 a.m. ET
today. Management will be joined by Richard
Auchus, M.D., Ph.D., Principal Investigator in the CAHtalyst
Adult study and Professor of Pharmacology and Internal Medicine,
Division of Metabolism, Endocrinology, and Diabetes at the
University of Michigan. Participants
can access the live conference call by dialing 800-895-3361 (U.S.)
or 785-424-1062 (International) using the conference ID: NBIX. The
webcast and supplementary materials for the call can also be
accessed on the Company's website under Investors at
www.neurocrine.com. A replay of the webcast will be available on
the website approximately one hour after the conclusion of the
event and will be archived for approximately one month.
About Classic Congenital Adrenal
Hyperplasia
Congenital adrenal hyperplasia (CAH) refers to a
group of genetic conditions that result in an enzyme deficiency
that alters the production of adrenal hormones which are essential
for life. Approximately 95% of CAH cases are caused by a mutation
that leads to deficiency of the enzyme 21-hydroxylase (21-OHD). In
classic CAH, severe deficiency of this enzyme leads to an inability
of the adrenal glands to produce cortisol and, in approximately 75%
of cases, aldosterone. If left untreated, classic CAH can result in
salt wasting, dehydration, and even death.
There are currently no non-glucocorticoid treatments approved by
the U.S. Food and Drug Administration (FDA) for classic CAH.
Glucocorticoids (GCs), the current standard of care, are used not
only to correct the endogenous cortisol deficiency but typically
used at greater than physiologic (supraphysiologic) doses to try to
suppress the high levels of corticotropin-releasing factor (CRF)
and adrenocorticotropic hormone (ACTH) that result in androgen
excess. However, glucocorticoid treatment at supraphysiologic doses
has been associated with serious and significant complications of
steroid excess, including metabolic issues such as weight gain and
diabetes, cardiovascular disease, and osteoporosis. Additionally,
long-term treatment with supraphysiologic GC doses may have
psychological and cognitive impact such as changes in mood and
memory. Androgen excess has been associated with abnormal bone
growth and development in pediatric patients, female health
problems such as acne, excess hair growth and menstrual
irregularities, testicular rest tumors in males, and fertility
issues in both sexes. To learn more about CAH, click here.
About Crinecerfont
Crinecerfont is an investigational,
oral, selective corticotropin-releasing factor type 1 receptor
(CRF1) antagonist being developed to reduce and control
excess adrenal androgens through a steroid-independent mechanism
for the treatment of congenital adrenal hyperplasia (CAH) due to
21-hydroxylase deficiency (21-OHD). Antagonism of CRF1
receptors in the pituitary has been shown to decrease
adrenocorticotropic hormone (ACTH) levels, which in turn decreases
the production of adrenal androgens and potentially the symptoms
associated with classic CAH. Our data demonstrates that lowering
androgen levels enables lower, more physiologic dosing of
glucocorticoids and thus could potentially reduce the complications
associated with exposure to greater than normal glucocorticoid
doses in patients with classic CAH.
To learn more about crinecerfont, click here.
About the CAHtalyst™ Pediatric Phase 3
Study
The CAHtalyst™ Phase 3 global registrational study was
designed to evaluate the safety, efficacy, and tolerability of
crinecerfont in children and adolescents (2–17 years of age) with
classic congenital adrenal hyperplasia (CAH) due to 21-OHD. The
study enrolled 103 female and male patients with CAH and consisted
of a 28-week randomized, double-blind, placebo-controlled period
followed by 24 weeks of open-label crinecerfont treatment and
optional open-label extension. The study started in July 2021, and the open-label treatment portion
is still ongoing.
For more information about the CAHtalyst Pediatric Phase 3
study, please visit ClinicalTrialsPediatric.gov.
For more information about the CAHtalyst Phase 3 study in adults
(ages 18 years of age and older), please visit
ClinicalTrialsAdult.gov.
About Neurocrine Biosciences, Inc.
Neurocrine Biosciences is a leading neuroscience-focused,
biopharmaceutical company with a simple purpose: to relieve
suffering for people with great needs, but few options. We are
dedicated to discovering and developing life-changing treatments
for patients with under-addressed neurological, neuroendocrine and
neuropsychiatric disorders. The company's diverse portfolio
includes FDA-approved treatments for tardive dyskinesia, chorea
associated with Huntington's disease, Parkinson's disease,
endometriosis* and uterine fibroids*, as well as a robust pipeline
including multiple compounds in mid- to late-phase clinical
development across our core therapeutic areas. For three decades,
we have applied our unique insight into neuroscience and the
interconnections between brain and body systems to treat complex
conditions. We relentlessly pursue medicines to ease the burden of
debilitating diseases and disorders, because you deserve brave
science. For more information, visit neurocrine.com, and
follow the company on LinkedIn, Twitter, and Facebook.
(*in collaboration with AbbVie)
NEUROCRINE is a registered trademark of Neurocrine
Biosciences, Inc. The Neurocrine logo and CAHtalyst are trademarks
of Neurocrine Biosciences, Inc.
Forward-Looking Statement
In addition to historical
facts, this press release contains forward-looking statements that
involve a number of risks and uncertainties. These statements
include, but are not limited to, statements regarding the clinical
results from, and our future development plans with respect to,
crinecerfont, as well as the therapeutic potential and clinical
benefits or safety profile of crinecerfont. Among the factors that
could cause actual results to differ materially from those
indicated in the forward-looking statements include: top-line data
that we report may change following a more comprehensive review of
the data related to the clinical studies and such data may not
accurately reflect the complete results of the clinical study;
risks that regulatory submissions for our products and/or product
candidates may not occur or be submitted in a timely manner; our
products and/or product candidates may not obtain regulatory
approvals; or that the U.S. Food and Drug Administration or
regulatory authorities outside the U.S. may make adverse decisions
regarding our products and/or product candidates; our products
and/or product candidates will not be found to be safe and/or
effective or may not prove to be beneficial to patients; that
development activities for our products and/or product candidates
may not be completed on time or at all; that clinical development
activities may be delayed for regulatory or other reasons, may not
be successful or replicate previous and/or interim clinical trial
results, or may not be predictive of real-world results or of
results in subsequent clinical trials; competitive products and
technological changes that may limit demand for our products;
uncertainties relating to patent protection and intellectual
property rights of third parties; our dependence on third parties
for development and manufacturing activities related to our
products and our product candidates, and our ability to manage
these third parties; our future financial and operating
performance; risks and uncertainties associated with the
commercialization of our products; and other risks described in the
Company's periodic reports filed with the Securities and Exchange
Commission, including without limitation the Company's quarterly
report on Form 10-Q for the quarter ended June 30, 2023. Neurocrine Biosciences disclaims
any obligation to update the statements contained in this press
release after the date hereof.
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