- CAHtalyst™ Phase 3 Baseline Characteristics Highlight
Limitations of Current CAH Treatment Paradigm in Children,
Adolescents and Adults
- Phase 2 Study for
Modified-Release Hydrocortisone in Adults with Adrenal
Insufficiency Demonstrated Participants Achieved Physiological
Morning Cortisol Levels after 4 Weeks
- Phase
3 Extension Study Data for Modified-Release Hydrocortisone in
Adults with CAH Demonstrated Reduction in Median Daily
Hydrocortisone Dose and an Increase in Responders at Levels ≤ 25
mg/day
SAN
DIEGO, May 14, 2024 /PRNewswire/ -- Neurocrine
Biosciences, Inc. (Nasdaq: NBIX) and Diurnal Ltd., a Neurocrine
Biosciences company, presented baseline data from the CAHtalyst™
Phase 3 studies of crinecerfont in adult and pediatric patients
with congenital adrenal hyperplasia (CAH), and modified-release
hydrocortisone (Chronocort®) data for a Phase 2 clinical
study (CHAMPAIN) in participants with primary adrenal insufficiency
and in a Phase 3 extension study in CAH. These data, along with
several additional posters were presented at the European Congress
of Endocrinology 2024 meeting in Stockholm.
CAHtalyst Phase 3 Pediatric and Adult Studies— Baseline
Characteristics
Baseline characteristics of the subjects who enrolled in the
CAHtalyst Pediatric Phase 3 study were presented (Poster# P225).
The study enrolled 103 subjects 4 to 17 years of age with a
medically confirmed diagnosis of CAH due to 21-hydroxylase
deficiency, with 52% male, mean age 12 years old, and majority in
Tanner stages 3-5. There was evidence indicating inadequate adrenal
androgen control in many of these patients despite supraphysiologic
glucocorticoid dosing. At baseline, more than a third of the
participants reported comorbidities of advanced bone age, early
puberty, and obesity. Hirsutism (excessive hair growth, 12%) and
irregular menses (12%) were reported in females, and testicular
adrenal rest tumors were identified in more than a third of
males.
Baseline characteristics of 182 adults with CAH enrolled in the
CAHtalyst Adult Phase 3 study were also presented (Poster# P423).
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.
"At baseline, many participants in the CAHtalyst Pediatric study
showed clinical evidence of elevated glucocorticoid doses and
adrenal androgen excess. Many exhibited obesity, advanced bone age,
and early puberty, all of which can negatively impact development
in childhood and adolescence," said Eiry W. Roberts, M.D., Chief
Medical Officer at Neurocrine Biosciences. "Baseline
characteristics in the CAHtalyst Phase 3 study in adults saw this
trend continue. 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. In both studies, adrenal androgen
and other steroid markers were elevated at baseline 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 adult and pediatric patients with CAH due to 21-hydroxylase
deficiency. Data from both studies supported two New Drug
Application submissions to the U.S. Food and Drug Administration in
April 2024.
Phase 2 Data of Modified-Release Hydrocortisone
(Chronocort®) in Primary Adrenal Insufficiency
The Phase 2 data of modified-release hydrocortisone (MRHC) in
adults with primary adrenal insufficiency (CHAMPAIN study)
demonstrated that participants receiving MRHC achieved a
physiological morning cortisol level after four weeks of treatment
(Abstract #4275, RC3.4). In the study, twice
daily MRHC developed by Diurnal was compared with
once-daily Plenadren (modified-release hydrocortisone) in patients
aged ≥ 18 years with confirmed primary adrenal insufficiency
(defined as morning pre-dose cortisol <50 nmol/L).
Of the 49 evaluable participants in the CHAMPAIN Phase 2 study
with primary adrenal insufficiency, 45 achieved a physiological
morning cortisol level after four weeks on MRHC compared to 2
participants after four weeks on Plenadren (P < 0.0001). The
mean (standard deviation) waking cortisol was 422.85 (203.50)
versus 36.98 (113.87) nmol/L, respectively.
"Treatment with modified-release hydrocortisone resulted in a
greater proportion of patients with a physiological morning
cortisol level than treatment with Plenadren in patients with
primary adrenal insufficiency," said Eiry W. Roberts, M.D., Chief
Medical Officer at Neurocrine Biosciences. "Further analyses will
test the hypothesis that waking with physiological cortisol levels
improves fatigue and quality of life in these patients."
Phase 3 Extension Study of Modified-Release Hydrocortisone
(Chronocort®) in Congenital Adrenal Hyperplasia
MRHC also demonstrated potential value in improving control of CAH
compared to current glucocorticoid treatment (Abstract #4271,
RC3.1). In a 48-month Phase 3 extension study, MRHC-treated
participants showed a reduction in the median daily hydrocortisone
dose from 30mg to 20mg. Participants were considered responders
when their 9:00 a.m.
17-hydroxyprogesterone level was ≤ 36 nmol/L or their
androstenedione level was ≤7 nmol/L while receiving MRHC ≤ 25
mg/day.
"The number of participants achieving responder status increased
after four years in the MRHC Phase 3 extension study in patients
with CAH. MRHC demonstrated improved control of CAH, with an
ability to closely replicate cortisol diurnal rhythm when compared
to current glucocorticoid treatment," Dr. Roberts added.
Neurocrine Biosciences abstracts presented at ECE 2024
included:
- Baseline Characteristics of Children and Adolescents with
Classic Congenital Adrenal Hyperplasia Enrolled in CAHtalyst
Pediatric, a Phase 3 Study of Crinecerfont, a
Corticotropin-Releasing Factor Type 1 Receptor Antagonist (Poster
#P225)
- Baseline Characteristics of Adults with Classic Congenital
Adrenal Hyperplasia Enrolled in CAHtalyst Adult, a Phase 3 Study of
Crinecerfont, a Corticotropin-Releasing Factor Type 1 Receptor
Antagonist (Poster #P423)
- CHAMPAIN study: Initial Results from a Phase II Study of
Efficacy, Safety and Tolerability of Modified-Release
Hydrocortisones: Chronocort® (Efmody®) versus
Plenadren, in Primary Adrenal Insufficiency (Abstract #4275, Rapid
Communication #RC3.4)
- Biochemical Control with Dose Reduction in Chronic
Glucocorticoid Therapy over 4 Years: A Phase III Extension Study of
Chronocort (Efmody®) in the Treatment of Congenital
Adrenal Hyperplasia (CAH) (Abstract #4271, Rapid Communication
#RC3.1)
- Incidence of Adrenal Crisis in Congenital Adrenal Hyperplasia
(CAH) Patients During a Prospective Monitored Long-Term study of
Modified-Release Hydrocortisone (MRHC) Capsules, (Efmody) (Poster
#P215)
- Morning Cortisol Levels in Patients with Established Primary
Adrenal Insufficiency (Poster #P13)
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 (21-OHD). 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 and the CAHtalyst
Studies
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 (CAH)
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.
The CAHtalyst™ Pediatric and Adult Phase 3 global registrational
studies are designed 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.
To learn more about crinecerfont and the CAHtalyst studies,
click here.
About Primary Adrenal Insufficiency
Primary adrenal
insufficiency is a chronic endocrine condition that occurs when the
body does not make enough of certain adrenal hormones, including
cortisol and often aldosterone. Glucocorticoids such as
hydrocortisone are used to replace the missing cortisol, but
typical dosing regimens do not match the natural diurnal rhythm of
the body's cortisol production.
About Modified-Release Hydrocortisone (MRHC)
Diurnal
Ltd. developed modified-release hydrocortisone, a preparation of
hydrocortisone that has been specifically designed to replicate the
natural circadian rhythm of cortisol, when given in a twice-a-day
"toothbrush" regimen, (administered last thing at night before
sleep and first thing in the morning on waking). In 2021,
modified-release hydrocortisone (EFMODY®) received
marketing authorization for the treatment of congenital adrenal
hyperplasia from the Medicines and Healthcare products Regulatory
Agency (MHRA) in Great Britain
(England, Wales, and Scotland) and from the European Commission in
the European Union. Neurocrine Biosciences acquired Diurnal Group
plc. in November 2022. A new drug
application for the modified-release hydrocortisone formulation has
not been submitted to the U.S. Food and Drug Administration.
About MRHC Phase 2 Study in Adrenal Insufficiency
(CHAMPAIN)
The CHAMPAIN Phase 2 clinical study compared the
efficacy, safety and tolerability of twice daily DNL0200
(Chronocort), a modified-release hydrocortisone, with once daily
Plenadren, a combination of immediate- and delayed-release
hydrocortisone (authorized for use in the European Union), over a
treatment period of up to 2 months in participants ≥18 years of age
and diagnosed with primary adrenal insufficiency.
About the Phase 3 Extension Study for MRHC in CAH
(DIUR-006)
The DIUR-006 Phase 3 open-label extension study
assessed the long-term efficacy, safety and tolerability of
twice-daily DNL0200 (Chronocort®), a modified-release
hydrocortisone in adults with CAH. The study was performed to build
on the results of feeder studies DIUR-003 (Phase 2 in adults with
CAH) and DIUR-005 (EU Phase 3 Registrational Open-Label Study of
Chronocort compared to standard of care in adults with CAH), to
evaluate the long-term safety of Chronocort and also its long-term
efficacy in improving control of serum androgen levels (using
17-OHP and A4 as biomarkers).
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, YOU DESERVE BRAVE
SCIENCE, CHRONOCORT and EFMODY are registered trademarks of
Neurocrine Biosciences, Inc. CAHtalyst is a trademark 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 certain of our products. Among the
factors that could cause actual results to differ materially from
those indicated in the forward-looking statements include: risks
that regulatory submissions for our products and/or product
candidates may not occur or be submitted in a timely manner, or
accepted for filing; 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 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-presented-baseline-data-from-the-cahtalyst-program-in-cah-and-study-data-for-modified-release-hydrocortisone-in-primary-adrenal-insufficiency-and-cah-at-ece-2024-302144009.html
SOURCE Neurocrine Biosciences, Inc.