SAN DIEGO, March 12, 2019 /PRNewswire/ -- Neurocrine
Biosciences, Inc. (NASDAQ: NBIX) today announced positive interim
results from a Phase II proof-of-concept study evaluating the
safety, tolerability, pharmacokinetics and pharmacodynamics of
NBI-74788, a proprietary corticotropin-releasing factor type 1
(CRF1) receptor antagonist, in adult patients with classic
congenital adrenal hyperplasia (CAH). The results from this ongoing
Phase II open-label study demonstrated a reduction of at least 50
percent from baseline in 17-hydroxyprogesterone (17-OHP) and
adrenocorticotropic hormone (ACTH) levels in more than 50 percent
of CAH patients treated with NBI-74788 for 14 days. Meaningful
reductions were also observed in other biomarkers, including
androstenedione. NBI-74788 was shown to be well tolerated with no
serious adverse events reported to date. The Company plans to meet
with the FDA to discuss the registration program for NBI-74788 in
adult and pediatric patients with CAH, a genetic disorder affecting
the adrenal glands.
"Patients with classic CAH currently have limited treatment
options besides more and more glucocorticoids. The management of
their genetic disorder is complex due to the highly variable
clinical features and response to therapy, which also changes over
time. Most patients receive supraphysiologic doses of
glucocorticoids chronically to manage their disease, which
frequently leads to serious long-term health consequences," said
Richard Auchus, M.D., Ph.D., the
study's lead investigator and Professor of Internal Medicine,
Division of Metabolism, Endocrinology & Diabetes at
University of Michigan Health System.
"The interim results from this Phase II study of NBI-74788 are
encouraging, as they indicate a clinically meaningful reduction in
key biomarkers. These data provide encouragement that NBI-74788 has
potential as a new treatment option to help patients avoid the
complications associated with current therapeutic options for
classic CAH."
Classic CAH is a rare genetic disorder caused by a deficiency of
the 21-hydroxylase enzyme, which alters the production of cortisol
and other adrenal steroids, leading to adrenal insufficiency,
overgrowth of the adrenal glands, and excess androgen levels.
Classic CAH can lead to adrenal crisis, virilization, hirsutism,
precocious puberty, fertility problems and abnormal
growth. The standard of care for classic CAH requires a
lifelong regimen with high-dose corticosteroids, which cause
additional serious long-term clinical problems, including bone
loss, Cushing's syndrome and metabolic issues.
"We are very encouraged by the positive interim results of
NBI-74788 in this Phase II proof-of-concept study demonstrating the
pharmacological effects of CRF1 antagonism on key biomarkers in
patients with CAH," said Eiry W. Roberts, M.D., Chief Medical
Officer at Neurocrine Biosciences. "We look forward to meeting with
the FDA to discuss the registration program to bring this potential
new treatment option to patients with classic CAH."
NBI-74788 Phase II Study Design
The NBI-74788 Phase
II clinical study is an open-label, multiple-dose, dose-escalation
study to assess the safety, tolerability, pharmacokinetics and
pharmacodynamics of NBI-74788 in approximately 30 adults with a
documented medical diagnosis of classic 21-hydroxylase deficiency
CAH. The study includes a sequential-cohort design with three
NBI-74788 dose cohorts, with each dose administered for 14
consecutive days.
About NBI-74788
NBI-74788 is a proprietary, potent, selective, orally-active,
non-peptide corticotropin-releasing factor type 1 (CRF1) receptor
antagonist under evaluation for the treatment of classic CAH.
Blockade of CRF receptors in the pituitary has been shown to
decrease the release of adrenocorticotropic hormone (ACTH), which
in turn decreases the production of adrenal steroids, including
androgens, and potentially the symptoms associated with CAH.
Research suggests that lowering ACTH levels could reduce the amount
of corticosteroid treatment necessary for CAH patients to thrive
and avoid the effects associated with long-term steroid therapy.
About Classic Congenital Adrenal Hyperplasia (CAH)
Classic CAH is a genetic disorder that results in an enzyme
deficiency that alters the production of adrenal steroids. Because
of this deficiency, the adrenal glands have little to no cortisol
biosynthesis resulting in a potentially life-threatening condition.
If left untreated, classic CAH can result in salt wasting,
dehydration and eventually death. Even with cortisol replacement,
persistent elevation of adrenocorticotropic hormone (ACTH) from the
pituitary gland results in excessive androgen levels leading to
virilization and menstrual irregularities in females; both males
and females may also experience precocious puberty, short stature,
hirsutism, acne and fertility problems. Classic CAH is a disease
that affects approximately 20,000 to 30,000 people in the United States.
There are currently no non-steroidal FDA-approved treatments for
classic CAH. Corticosteroids, the current standard of care, are
used to both correct the endogenous cortisol deficiency and reduce
the excessive ACTH levels and androgen excess. However, the dose
and duration of steroid use required to suppress ACTH is well above
the normal physiological level of cortisol, which can result in
serious and common complications, including metabolic issues, bone
loss, growth impairment, and iatrogenic Cushing's syndrome.
About Neurocrine Biosciences
Neurocrine
Biosciences, a San Diego based biopharmaceutical company,
is focused on developing treatments for neurological and endocrine
related disorders. The company discovered, developed and markets
INGREZZA® (valbenazine) capsules, the
first FDA-approved product indicated for the treatment of
adults with tardive dyskinesia, an involuntary movement disorder.
Discovered and developed through Phase II clinical trials by
Neurocrine, ORILISSA® (elagolix), the
first FDA-approved oral medication for the management of
endometriosis with associated moderate to severe pain in over a
decade, is marketed by AbbVie as part of a collaboration
to develop and commercialize elagolix for women's health.
Neurocrine's clinical development programs include opicapone as an
adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in
Parkinson's disease patients, elagolix for uterine fibroids
with AbbVie, valbenazine for the treatment of Tourette
syndrome, and NBI-74788 for the treatment of congenital adrenal
hyperplasia (CAH). For more information and the latest updates
from Neurocrine Biosciences, please
visit www.neurocrine.com.
Forward-Looking Statements
In addition to historical facts, this press release may contain
forward-looking statements that involve a number of risks and
uncertainties. Among the factors that could cause actual results to
differ materially from those indicated in the forward-looking
statements are risks and uncertainties associated with Neurocrine's
product candidate NBI-74788 and the Phase II study in general,
including the risk that NBI-74788 will not be found to be safe
and/or effective, or that final results of the study will replicate
the interim results. Specifically, the risks and uncertainties the
Company faces for NBI-74788 include risks that development
activities may not be completed on time or at all; risks 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;
risks that regulatory submissions may not occur or be submitted in
a timely manner; risks that NBI-74788 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 the Company's product candidates; 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-K for the year ended
December 31, 2018. Neurocrine
disclaims any obligation to update the statements contained in this
press release after the date hereof.
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SOURCE Neurocrine Biosciences, Inc.