Neurocrine Biosciences Announces Successful Elagolix PETAL Study in Endometriosis

Neurocrine Biosciences Announces Successful Elagolix PETAL Study in
Endometriosis
Phase II Study Meets Primary Bone Mineral Density and Secondary Efficacy
Endpoints

SAN DIEGO, Sept. 2 /PRNewswire-FirstCall/ -- Neurocrine Biosciences, Inc.
(Nasdaq: NBIX) today announced positive safety and efficacy results from its
third Phase II clinical trial using its proprietary, orally-active nonpeptide
Gonadotropin-Releasing Hormone (GnRH) receptor antagonist, elagolix, in
patients with endometriosis. The PETAL study enrolled 252 patients, with a
confirmed diagnosis of endometriosis, into three treatment groups; elagolix
150 mg once daily, elagolix 75 mg twice daily, or depo-subQ provera 104(TM)
(DMPA) for six months of treatment.
The primary endpoint for the PETAL study was the percent change from
baseline in mean bone mineral density (BMD) at Month 6 measured via dual
energy X-ray absorptiometry (DXA). Pursuant to discussion with the FDA, the
pre-specified statistical analysis plan sought to demonstrate that at Month 6,
the lower bound of the 95% confidence interval did not exceed a -2.2% change
in BMD from baseline. In women randomized to elagolix 150 mg once daily, the
mean percent change from baseline at Month 6 was -0.11% for the spine (lower
bound -0.70%) and -0.47% for the femur (lower bound -0.96%). The mean percent
change from baseline at Month 6 for the elagolix 75 mg twice daily dosing arm
was -1.30% for the spine (lower bound -1.86%) and -0.99% for the femur (lower
bound -1.46%).
"The PETAL study demonstrates that elagolix did not induce significant
bone loss over a six month treatment of patients with endometriosis, while
providing both rapid and significant pain reduction in endometriosis
symptoms," said Chris O'Brien, MD, Chief Medical Officer at Neurocrine.
"Additionally, this study confirms our decision to move forward with once
daily dosing."
Secondary endpoints for the PETAL study were evaluated to assess the
improvement of endometriosis symptoms following treatment with elagolix.
Improvement in endometriosis symptoms was documented using several different
scales for endometriosis pain. The following were assessed before, during and
after the six months of treatment:
-- Total Composite Pelvic Sign and Symptoms Score (CPSSS), a validated
0-15 scale that assesses five components of endometriosis pain
severity, each on a 0-3 scale.
-- Dysmenorrhea (pelvic pain during menstruation), a component of the
CPSSS; 0-3 scale (0=absence of pain, 1=mild pain, 2=moderate pain,
3=severe pain)
-- 98% of patients at baseline had moderate or severe dysmenorrhea.
-- Non-menstrual pelvic pain (pelvic pain outside of menstruation), a
component of the CPSSS; 0-3 scale (0=absence of pain, 1=mild pain,
2=moderate pain, 3=severe pain)
-- 97% of patients at baseline had moderate or severe non-menstrual
pelvic pain.
-- Responder Rate, percentage of patients who had a one point or greater
decrease in pain score.
-- Visual Analog Scale (VAS) to assess pelvic pain levels using daily
electronic diary.

Elagolix provided a clinically meaningful and statistically significant
reduction in endometriosis pain from baseline as shown below. The magnitude of
improvement is comparable to that demonstrated with the currently approved
agents, leuprolide and DMPA.

Screening Elagolix
Baseline 150mg qd 75mg bid DMPA
CPSSS 9.1
Week 4 mean -3.9* -3.7* -3.8*
Week 24 mean -5.5* -5.2* -5.3*
Dysmenorrhea 2.4
Week 24 mean -1.5* -1.4* -1.7*
Responder Rate 86% 74% 86%
Non-Menstrual Pelvic
Pain 2.2
Week 24 mean -1.2* -1.2* -1.1*
Responder Rate 86% 77% 77%
VAS 78.7
Week 24 mean -31.8* -33.4* -35.5*

*ITT Analysis, p<0.0001

"We have treated over 600 subjects with elagolix in our extensive
endometriosis clinical program, and have consistently seen a robust reduction
in endometriosis pain using multiple outcome measures. In our previous Phase
II studies we have shown rapid onset of action and sustained efficacy over
three months. This study extends those findings, demonstrating significant
and sustained pain reduction for six months," said Dr. O'Brien. "There is much
more data to come from this study once patients complete the six month
follow-up and the study is unblinded at an individual patient level. At that
time we will be able to make correlations between pain scores, BMD,
pharmacokinetic values, and hormonal levels on an individual patient basis,
and we look forward to also sharing those results, as soon as they are
available."
Treatment with elagolix was also safe and generally well tolerated.
Discontinuation from the clinical trial due to adverse events (AE) was more
common among women randomized to DMPA (16%) than those receiving elagolix 150
mg once daily (5%) or 75 mg twice daily (7%). This increased discontinuation
in women randomized to DMPA was primarily attributable to irregular vaginal
bleeding. The overall rate of AE reporting was comparable across all groups.
The most common AE was headache; this was reported 35 times by 19 women (23%)
randomized to elagolix 150 mg once daily, 52 times by 22 women (26%)
randomized to elagolix 75 mg twice daily, and 43 times by 12 (14%) women
randomized to DMPA. There were two serious AEs that led to discontinuation
from the trial, both in the DMPA group. The mean frequency of hot flashes was
comparable in both the screening period and the treatment period,
approximately 0.5 per day across all treatment groups, consistent with our
prior Phase II studies.
"We couldn't be more pleased with the results of this study," said Kevin
C. Gorman, President and Chief Executive Officer, Neurocrine Biosciences. "We
began this program nine years ago with the hope of selectively modulating the
GnRH system with an oral antagonist. This trial and our previous Phase II
studies have now shown that this is possible. Elagolix is a first in class
drug for endometriosis sufferers who desperately need a safe and effective
therapy. This is apparent from the 8,000 inquiries to the call center for just
this one study. Additionally, to date we had more than 6,000 inquiries
regarding the ongoing Lilac PETAL study which is now fully enrolled and on
track to report results in 2009."
"These study results are very encouraging," said Shayne M. Plosker, MD,
Associate Professor and Division Director, of USF IVF and Reproductive
Endocrinology at the University of South Florida College of Medicine in Tampa.
"Elagolix has the potential to be an ideal advanced medical therapy for
endometriosis-associated pelvic pain and dysmenorrhea. Intermediate
suppression of estradiol by a well-tolerated drug appears attainable affording
endometriosis symptom reduction without bone loss."
Neurocrine Biosciences would like to thank the patients and the
investigators for participating in this important clinical trial.
Conference Call and Webcast Information
The Company will host a live conference call and webcast to provide
additional details of this study tomorrow, Wednesday, September 3, 2008 at
8:30 a.m. Eastern Time (5:30 a.m. Pacific Time). Participants can access the
live conference call by dialing 1-800-894-5910 (US) or 785-424-1052
(International) using the conference ID: 7GNRH. The call can also be accessed
via the webcast through the Company's website at http://www.neurocrine.com.
If you are unable to attend the Webcast and would like further information
on this announcement please contact the Investor Relations Department at
Neurocrine Biosciences at (858) 617-7600. A replay of the Conference Call will
be available approximately one hour after the conclusion of the call by
dialing 1-800-374-0934 (US) or 402-220-0680 (International) using the
conference ID: 7GNRH. The call will be archived for two weeks.
Neurocrine Biosciences, Inc. is a biopharmaceutical company focused on
neurological and endocrine diseases and disorders. Our product candidates
address some of the largest pharmaceutical markets in the world including
endometriosis, irritable bowel syndrome (IBS), anxiety, depression, pain,
diabetes, benign prostatic hyperplasia (BPH) and other neurological and
endocrine related diseases and disorders. Neurocrine Biosciences, Inc. news
releases are available through the Company's website via the internet at
http://www.neurocrine.com.
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, as well as
risks and uncertainties associated with the Company's GnRH program and Company
overall. Specifically, the risks and uncertainties the Company faces with
respect to the Company's GnRH program include, but are not limited to, risk
that the Company's elagolix Phase II clinical trials will fail to demonstrate
that elagolix is safe and effective; risk that elagolix will not proceed to
later stage clinical trials; risk associated with the Company's dependence on
corporate collaborators for development, commercial manufacturing and
marketing and sales activities. With respect to its pipeline overall, the
Company faces risk that it will be unable to raise additional funding required
to complete development of all of its product candidates; risk relating to the
Company's dependence on contract manufacturers for clinical drug supply; risks
associated with the Company's dependence on corporate collaborators for
commercial manufacturing and marketing and sales activities; uncertainties
relating to patent protection 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 products; and
the other risks described in the Company's report on Form 10-K for the year
ended December 31, 2007 and reports on Form 10-Q for the quarters ended March
31, 2008 and June 30, 2008. Neurocrine undertakes no obligation to update the
statements contained in this press release after the date hereof.
SOURCE Neurocrine Biosciences, Inc.

Claudia Woodworth of Neurocrine Biosciences, +1-858-617-7600