Neurocrine Biosciences,
Inc. (Nasdaq: NBIX) today announced positive results of its 'proof of
concept', safety, efficacy and dose-finding Phase II clinical trial using
its proprietary, orally-active small molecule Gonadotropin-Releasing
Hormone (GnRH) receptor antagonist (NBI-56418).
The 3-month data comes from a multi-center, randomized, double-blind,
placebo-controlled trial involving patients with a confirmed diagnosis of
endometriosis. The study followed a parallel-group design in which 76
subjects were randomized to one of three treatment groups: placebo, 75 mg
of NBI-56418, or 150 mg of NBI-56418 each administered once daily. Dosing
started on Day 2 to Day 7 of the menstrual cycle and continued over 12
weeks with assessments of symptoms and signs of disease conducted at 4-week
intervals using the Composite Pelvic Sign and Symptoms Score (CPSSS).
Assessment of pain intensity was measured daily by a Visual Analog Scale
(VAS) and collected by electronic diary. Full data regarding treatment
impact on menses, hormones and a variety of metabolic biomarkers will be
available at the completion of the ongoing 3-month safety follow-up period.
The primary endpoint of the study was reduction in the CPSSS, a
validated clinical endpoint assessing subjective and objective elements of
endometriosis. For the CPSSS, which has a maximum possible value of 15,
mean values at baseline were 9.1, 8.5 and 8.0 for the placebo, 75 mg and
150 mg groups respectively. After treatment, there were reductions of 3.7
(placebo), 3.9 (75 mg) and 5.0 (150 mg) points in the score at week 12.
A patient-completed VAS was used to record pain intensity on a daily
basis. Mean values for each 4-week interval were analyzed. This reveals
dose-related improvements of 5 (placebo), 14 (75 mg) and 21 (150 mg) from
baseline means of 31.2, 34.9 and 33.5 respectively. From a safety
perspective, preliminary information on the adverse event rates show that
there is little difference in the percentage of patients with an adverse
event across treatment groups. Treatment-related adverse events occurred in
39%; 36%; and 26% of the patients in the placebo, 75 mg and 150 mg groups
respectively. There was no increase in hot flashes in the NBI-56418 treated
groups compared with placebo.
"We are pleased with the results demonstrating a robust treatment
effect with NBI-56418 as shown by two clinical outcome measures. The
reductions in scores at the highest dose were at the levels expected for
peptide agonists such as Lupron Depot(R), which while efficacious, can lead
to numerous undesirable side effects and limit utility. While not fully
analyzed, preliminary results show that our GnRH antagonist demonstrated
reductions in pain scores at the earlier time points in the study," said
Chris O'Brien, M.D., Senior Vice President of Clinical Development for
Neurocrine Biosciences.
"We have met our 'proof of concept' criteria in the clinical setting
with our GnRH antagonist. Since the effects of estradiol reduction have
been previously well correlated with a reduction of pain and other symptoms
of endometriosis, we believe our oral GnRH antagonist will have significant
therapeutic application in endometriosis. These new data are encouraging
and suggest that sufficient estradiol suppression has been achieved for
pain reduction while potentially avoiding reduction in bone mineral density
and the other undesirable metabolic consequences of GnRH agonist
therapies," said Wendell Wierenga, Ph.D. Executive Vice President of
Research and Development for Neurocrine Biosciences.
"Based on these data, we are moving ahead to select the dosing regimen
for an expanded six-month study in patients with endometriosis. This Phase
IIb study will include several hundred patients and is expected to be
initiated in the 3rd Quarter of 2006," added Wierenga.
Additional Phase II Clinical Studies Underway with GnRH for
Endometriosis
Neurocrine is continuing to enroll patients in a second Phase II study
in patients with endometriosis that was initiated in December 2005 to
explore once vs. twice daily dosing. This study, a multi-dose,
double-blind, placebo-controlled trial, is enrolling 72 patients and is
designed to assess safety and efficacy over a three-month period. The
primary endpoint of reduction in endometriotic pain will be measured by the
CPSSS. Preliminary results are expected to be announced in the 4th Quarter
of 2006.
Neurocrine will be initiating a Phase IIb study in the 3rd quarter of
2006 in which patients with endometriosis will receive NBI-56418 for six
months. In addition to confirming the effect of NBI-56418 on endometriotic
pain, this study is designed to assess the impact of treatment on bone
mineral density. The six-month results, together with data from ongoing
Phase II studies will be the basis for securing agreement to a registration
plan acceptable to the FDA, estimated to occur next year. Finally, the
company recently started a Phase I study in male volunteers as part of the
Benign Prostate Hyperplasia development program. The Company expects to
provide more details on the six month trial together with ongoing results
from the Phase I trial in the 3rd Quarter of 2006.
Background
Nearly 7 million women in the US have endometriosis, many with severe
or moderate symptoms. Many patients are believed to be misdiagnosed or
undiagnosed. The impact of endometriosis on the lives of sufferers can be
significant -- adversely affecting the ability of patients to maintain
relationships and employment.
Surgery and medical treatments are currently available for women with
endometriosis. Surgery is not acceptable to many patients. Although
indicated for endometriosis, medical therapies such as the injectable GnRH
agonists leuprolide or injectable progesterone are associated with a range
of potentially unacceptable side effects including bone loss. Consequently,
prescribing physicians often reserve these medical interventions for
patients with severe endometriosis. For the majority of endometriosis
patients suffering from moderate or mild symptoms, the remaining treatment
options, oral contraceptives and analgesics, are only partially effective.
Based on the large number of endometriosis sufferers and the
significant level of unmet need, we believe a highly attractive commercial
opportunity exists for a new product that is able to offer patients and
prescribers effective control of endometriosis symptoms with limited side
effects.
Neurocrine Biosciences, Inc. is a product-based biopharmaceutical
Company focused on neurological and endocrine diseases and disorders. Our
product candidates address some of the largest pharmaceutical markets in
the world including insomnia, anxiety, depression, diabetes, irritable
bowel syndrome, and autoimmunity. Neurocrine Biosciences, Inc. news
releases are available through the Company's website via the Internet at
neurocrine
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 business and finances in
general including the risks and uncertainties associated with, or arising
out of, drug discovery, pre-clinical and clinical development of
pharmaceutical products. Specifically, the Company faces risks and
uncertainties arising out of it GnRH clinical development program including
risk that its lead candidate, NBI-56418, will not proceed to later stage
clinical trials; risk that should NBI-56418 may prove unsuitable for
continued development, the Company will not be successful in identifying
alternative GnRH antagonist products that are safe and effective; risk
relating to the Company's dependence on contract manufacturers for GnRH
antagonist product clinical drug supply and compliance with regulatory
requirements for marketing approval; risks that the Company may be
dependent on corporate collaborators for commercial manufacturing and
marketing and sales activities for its GnRH antagonist products;
uncertainties relating to patent protection for the Company's GnRH
antagonist products and intellectual property rights of third parties;
risks and uncertainties relating to competitive products and technological
changes that may limit demand for the Company's GnRH antagonist products;
risk that the Company will be unable to raise additional funding required
to complete development of its GnRH antagonist product candidates; and the
other risks described in the Company's report on Form 10-K for the year
ended December 31, 2005. Neurocrine undertakes no obligation to update the
statements contained in this press release after the date hereof.
Neurocrine Biosciences, Inc.
neurocrine
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