STUDY CONFIRMS EFFICACY IN VALIDATED ENDPOINTS; MIXED RESULTS IN
EXPLORATORY ENDPOINTS
COMPANY TO HOST CONFERENCE CALL AND WEBCAST THURSDAY, MARCH 26TH AT 8:00AM
ET / 5:00AM PT
SAN DIEGO, March 25 /PRNewswire-FirstCall/ -- Neurocrine Biosciences, Inc.
(Nasdaq: NBIX) today announced top-line efficacy and safety results from its
fourth Phase II clinical trial using its proprietary, orally-active nonpeptide
Gonadotropin-Releasing Hormone (GnRH) receptor antagonist, elagolix, in
patients with endometriosis. The 702 study (Lilac PETAL study) randomized 155
patients with a confirmed diagnosis of endometriosis into three treatment
arms; elagolix 150 mg once daily, elagolix 250 mg once daily, or placebo.
After completion of the initial three months of treatment, placebo recipients
were re-randomized to elagolix for an additional three months. The top-line
results reflect the three-month placebo-controlled portion of the study.
"It is clear from this study and all of our previous studies that elagolix
is a safe and effective treatment for endometriosis sufferers," said Kevin
Gorman, President and Chief Executive Officer of Neurocrine Biosciences.
"This Phase II study provides the information we need to continue to move this
program forward. While limitations were discovered in some of the new
exploratory efficacy measures, elagolix again showed strong efficacy in the
historical validated endometriosis measures, with an excellent safety
profile."
The Lilac PETAL study assessed endometriosis pain through a variety of
measures, several of which were never before utilized in an endometriosis
trial. These exploratory endpoints included three daily assessments using an
electronic diary: a numeric rating scale (NRS) for pain (scale 0-10); a
dysmenorrhea pain assessment (scale 0-3); and a non-menstrual pelvic pain
assessment (scale 0-3). The NRS is the pain assessment scale suggested by the
National Institutes of Health (NIH) and the American Society of Reproductive
Medicine. The dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP)
assessments were suggested by the Food and Drug Administration (FDA). The
trial also utilized two validated efficacy endpoints consisting of the Patient
Global Impression of Change (PGIC), an assessment of the changes in
endometriosis-related pain; and the Endometriosis Health Profile 5 (EHP-5), a
disease specific quality of life scale.
The top-line data confirm that elagolix provides endometriosis sufferers
with clinical improvement of symptoms, coupled with an excellent safety and
tolerability profile. However, certain aspects of the exploratory endpoints,
used as an alternative to the validated Composite Pelvic Signs and Symptoms
Scale (CPSSS), require additional dialogue with our expert advisors and
regulatory authorities.
Efficacy Endpoints: Mean
Change From Baseline to Week 12 Placebo 150 mg 250 mg
Numeric Rating Scale (mean daily pain, 0-10) -0.90 -1.19 -1.25
Numeric Rating Scale (peak pain, 0-10) -1.33 -2.45* -2.75**
Non-Menstrual Pelvic
Pain (mean daily pain, 0-3) -0.24 -0.27 -0.25
Dysmenorrhea (mean daily pain, 0-3) -0.27 -0.68** -0.76**
Endometriosis Health
Profile (pain dimension, 0-100) -11 -23* -20***
Efficacy Endpoints: Status at Week 12
Patient Global
Impression of
Change (mean score, 1-7) 3.2 2.2** 2.3**
Patient Global
Impression of
Change (% subjects score < /=2) 33% 67%** 62%**
*p<0.05, **p<0.01, ***p=0.068
As shown with all previous elagolix trials, symptoms of dysmenorrhea
improved significantly in both elagolix treatment groups compared to placebo
(elagolix 150 mg, p<0.01; elagolix 250 mg, p<0.001). Additionally, the
percentage of dysmenorrhea pain-free days was markedly higher in the elagolix
treatment groups when compared to placebo (elagolix 150 mg, p=0.0012; elagolix
250 mg, p=0.0002).
The impact of elagolix treatment on "worst pain" is evident when examining
the monthly peak NRS. Statistically significant improvement was documented
for elagolix 150 mg (p< 0.05) and elagolix 250 mg (p<0.005) compared to
placebo.
The PGIC utilizes a standard 7-point Likert scale spanning "Very Much
Worsened" to "Very Much Improved" ("No Change"=4) to assess the change in
endometriosis-related pain. Clinically meaningful and statistically
significant improvement was documented at all time points for either dose of
elagolix compared to placebo, even when using the conservative definition of
"Much Improved" or "Very Much Improved" (p<0.05 at Weeks 4 and 8, p<0.01 at
Week 12).
Subjects treated with elagolix also reported improvement compared to
placebo on the EHP-5 core domain of endometriosis pain, a validated
endometriosis-specific scale which documents the impact of treatment on a
variety of health outcome domains. Statistical significance (p< 0.05) for the
core pain domain was demonstrated at Weeks 8 and 12 for elagolix 150 mg and at
Week 8 for elagolix 250 mg (Week 12 value, p=0.068).
Two of the exploratory scales (daily NRS and non-menstrual pelvic pain,
each averaged monthly) were relatively insensitive to treatment effects.
Although the daily pain scores improved numerically over the course of
treatment on the primary endpoint NRS, the change from baseline was not
statistically significant compared to placebo. The non-menstrual pelvic pain
score of 0.9 was low at baseline and decreased across all treatment groups by
approximately -0.25 points. The results from both of these two exploratory
scales are in direct contrast to the statistically significant results of the
validated PGIC and EHP-5 pain dimension.
To better understand this observation, we examined treatment effects in
subjects with moderate or greater pain (CPSSS non-menstrual pelvic pain score
at baseline >/=2); which accounted for two-thirds of the subjects (n=95). For
these subjects, both elagolix treatment arms were superior to placebo on a
composite of the FDA-suggested daily scales (total score DYS + NMPP): elagolix
150 mg, p=0.0305 and elagolix 250 mg, p=0.0440. This observation suggests
that changes in the exploratory FDA composite scale is clinically relevant in
women with dysmenorrhea and non-menstrual pelvic pain (if moderate or severe
at baseline) and confirms the effect of elagolix as shown with the validated
endpoints. It also suggests that the NMPP component of the FDA exploratory
scale may not be useful in assessing patients with mild endometriosis
symptoms.
"This is the first time that we have assessed the exploratory endpoints
suggested by the FDA and the NIH," said Dr. Chris O'Brien, Chief Medical
Officer of Neurocrine Biosciences. "The decoupling of these exploratory daily
scales from the established monthly validated scales will prompt us to seek
input from regulatory authorities and our expert clinical consultants. Most
importantly, this trial replicated our previous results with women recognizing
significant improvement in endometriosis symptoms across multiple time points
and elagolix doses."
Safety Profile
Elagolix was generally safe and well tolerated; the frequency of
treatment-related adverse events was 8% in the placebo group and 14 and 15% in
the two elagolix treatment groups. There were no serious adverse events
during the treatment period. The two most common adverse events were headache
and nausea, which were typically mild and transient. Consistent with previous
clinical studies, elagolix showed a dose dependent decrease in mean estradiol
levels and minimal impact on bone mineral density and related serum
n-telopeptide levels during the initial three months of treatment.
Conference Call and Webcast Information
The Company will host a live conference call and webcast to provide
additional details of this study tomorrow morning, Thursday March 26, 2009 at
8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access the
live conference call by dialing 1-800-862-9098 (US) or 785-424-1051
(International) using the conference ID: 7GNRH1. 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 1-800-723-0528 (US) or 402-220-2654 (International) using the
conference ID: 7GNRH1. 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, anxiety, depression, pain, diabetes, benign prostatic
hyperplasia (BPH), irritable bowel syndrome (IBS) 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, 2008. Neurocrine undertakes no obligation to update the
statements contained in this press release after the date hereof.
SOURCE: Neurocrine Biosciences, Inc.
CONTACT:
Claudia Woodworth of Neurocrine Biosciences,
+1-858-617-7600
Web Site: http://www.neurocrine.com