- CAHtalyst™ Study Baseline Characteristics Highlight the Need
for New Treatment Options to Reduce Adrenal Androgens and
Supraphysiologic Glucocorticoid Dosing in CAH Adult Patients
- Comprehensive Literature Review Identified Potential
Psychological and Cognitive Impact of High Glucocorticoid Doses in
CAH Patients
SAN
DIEGO, May 9, 2024 /PRNewswire/ -- Neurocrine
Biosciences, Inc. (Nasdaq: NBIX) today announced that it will
present CAHtalyst™ Adult Phase 3 clinical study baseline
characteristics for adults with congenital adrenal hyperplasia
(CAH) enrolled in the study, as well as data from a comprehensive
literature review assessing the impact of supraphysiologic
glucocorticoid (GC) doses on psychiatric disorders and cognition in
patients with CAH.
The CAHtalyst Adult study baseline data demonstrate the
potential long-term consequences of current CAH treatments, with
many patients in young adulthood experiencing disorders found more
commonly in people decades older, including osteopenia,
hypertension and hyperlipidemia. In addition, the results of a
comprehensive literature review showed that many CAH patients
receiving supraphysiologic GC doses had an increased risk of
psychiatric and cognitive symptoms. These new data were presented
at oral presentations and poster sessions at the American
Association of Clinical Endocrinology 2024 Annual Meeting in
New Orleans.
CAHtalyst Phase 3 Adult Study Baseline Characteristics
Baseline characteristics of 182 adults with CAH enrolled in the
CAHtalyst Adult Phase 3 study were summarized in an oral
presentation at the conference by Oksana
Hamidi, M.D., Associate Professor in the Division of
Endocrinology and Metabolism at UT Southwestern Medical Center.
Despite supraphysiologic GC dosing, levels of
adrenocorticotropic hormone, 17-hydroxyprogesterone and
androstenedione (A4) were elevated at baseline, with levels of
testosterone (females) and A4/testosterone (males) also elevated.
Common comorbidities included anxiety, osteopenia, depression,
hypertension and hyperlipidemia. Overall, close to half of
participants were overweight. Forty-seven percent of females
reported a history of hirsutism (excessive hair growth) and acne
(23%), and testicular adrenal rest tumors were identified in 66% of
male participants.
"In the CAHtalyst Phase 3 study in adults, we're seeing the
consequence of decades of living with CAH and the clinical
consequences of the current treatment paradigm in the baseline
characteristics," said Eiry W. Roberts, M.D., Chief Medical Officer
at Neurocrine Biosciences. "Despite being in their 30s, many of the
CAHtalyst Adult study participants have been diagnosed with
disorders that are more common in people twice their age, including
osteopenia, hypertension and hyperlipidemia. As we saw in the
CAHtalyst Pediatric study baseline data presented at PES2024,
adrenal androgen and other steroid markers were also elevated
despite supraphysiologic doses of glucocorticoids, demonstrating
the need for novel glucocorticoid-independent approaches to
reducing adrenal androgens and supraphysiologic glucocorticoid
dosing in CAH patients at all ages."
In 2023, Neurocrine Biosciences announced top-line data from the
CAHtalyst Pediatric and CAHtalyst Adult Phase 3 clinical studies
evaluating the efficacy, safety, and tolerability of crinecerfont
in children, adolescents, and adults with CAH due to 21-hydroxylase
deficiency. The data from both studies supported two New Drug
Applications submitted to the U.S. Food and Drug Administration in
April 2024.
Literature Review: Psychological and Cognitive Impact of
Supraphysiologic Glucocorticoids
Neurocrine Biosciences also presented the results of a
comprehensive review of available literature between 1996–2023
focusing on the use of supraphysiologic doses of hydrocortisone and
their effect on psychiatric disorders and cognition in patients
with CAH (Poster# 05). The review identified mood and psychotic
disorders as the most consistent psychiatric disorders seen. Brain
morphology in patients with CAH was altered (white matter
microstructure abnormalities), suggesting an increased risk of
cognitive impairment with use of supraphysiologic doses of GCs in
these patients.
"Glucocorticoids administered at supraphysiologic doses can lead
to a spectrum of psychiatric and cognitive symptoms, with the
severity correlating with the glucocorticoid dosage given," said
Amy Wisniewski, M.D., Research
Professor, Psychology at Oklahoma State
University. "As a result, increased awareness among
healthcare providers is necessary to monitor CAH patients receiving
supraphysiologic doses of glucocorticoids for signs of psychiatric
and cognitive symptoms. More research is needed to identify the
multiple factors, including prolonged exposure to adrenal androgen
excess and glucocorticoid-induced deterioration of brain regions,
that may determine the cognitive impairment of patients with
CAH."
Neurocrine Biosciences abstracts to be presented at the meeting
include:
- Baseline Characteristics of Adults with Classic Congenital
Adrenal Hyperplasia Enrolled in CAHtalyst, a Phase 3 Study of
Crinecerfont, a Corticotropin-Releasing Factor Type 1 Receptor
Antagonist, Oral Presentation—Dr. Oksana
Hamidi, May 10; 11:00-11:15 a.m.
- The Psychological and Cognitive Impact
of Supraphysiological Glucocorticoids in Patients with
Congenital Adrenal Hyperplasia: A Comprehensive Review,
May 11; 7:30–7:45 a.m. (Poster
#05)
- Glucocorticoid Treatment Patterns in Pediatric and Adult
Patients with Classic Congenital Adrenal Hyperplasia: Results from
the CAHtalog™ Registry, May 10;
10:10–10:25 a.m. (Poster #14)
About Congenital Adrenal Hyperplasia
Congenital
adrenal hyperplasia (CAH) is a rare genetic condition that results
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. 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, CAH can
result in salt wasting, dehydration, and even death.
Glucocorticoids (GCs) are currently used not only to correct the
endogenous cortisol deficiency, but doses used are higher than
cortisol replacement needed (supraphysiologic) to lower the levels
of adrenocorticotropic hormone (ACTH) and adrenal androgens.
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. Adrenal 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 glucocorticoid-independent
mechanism for the treatment of congenital adrenal hyperplasia due
to 21-hydroxylase deficiency. Antagonism of CRF1
receptors in the pituitary has been shown to decrease
adrenocorticotropic hormone levels, which in turn decreases the
production of adrenal androgens and potentially the symptoms
associated with CAH. Our data demonstrate that lowering adrenal
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 CAH.
To learn more about crinecerfont, click here.
About the CAHtalyst™ Phase 3 Studies
The
CAHtalyst™ Pediatric and Adult Phase 3 global studies are the
largest registrational studies conducted to date to evaluate the
safety, efficacy, and tolerability of crinecerfont in children and
adolescents, and adults respectively, with congenital adrenal
hyperplasia due to 21-hydroxylase deficiency. The primary portions
of the CAHtalyst Phase 3 studies have completed and enrollment is
closed, while the open-label treatment portions of both
studies are 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, 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, X
(formerly Twitter), and Facebook.
(*in collaboration with AbbVie)
The NEUROCRINE BIOSCIENCES Logo Lockup and YOU DESERVE BRAVE
SCIENCE are registered trademarks of Neurocrine Biosciences, Inc.
CAHtalyst and CAHtalog are trademarks of Neurocrine Biosciences,
Inc.
Forward-Looking Statements
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 potential
benefits to be derived from crinecerfont. Among the factors that
could cause actual results to differ materially from those
indicated in the forward-looking statements include: the
crinecerfont NDAs may not be accepted for filing by the FDA or may
not obtain regulatory approval or such approval may be delayed;
additional regulatory submissions may not occur or be submitted in
a timely manner; the FDA may make adverse decisions regarding
crinecerfont; crinecerfont may not be found to be safe and/or
effective or may not prove to be beneficial to patients;
development activities for crinecerfont may not be completed on
time or at all; 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 crinecerfont, 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 March 31, 2024. Neurocrine Biosciences disclaims
any obligation to update the statements contained in this press
release after the date hereof.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-cahtalyst-adult-study-baseline-characteristics-and-data-on-impact-of-supraphysiologic-glucocorticoid-therapy-at-aace-2024-302140485.html
SOURCE Neurocrine Biosciences, Inc.