Elagolix Successful in Six Month Lilac Petal Study; Safety and Efficacy Confirmed in Patients With Endometriosis
SAN DIEGO, July 29 /PRNewswire-FirstCall/ -- Neurocrine
Biosciences, Inc. (NASDAQ:NBIX)
today announced new six month safety and efficacy results from its
fourth Phase II clinical trial using its proprietary, orally-active
non-peptide Gonadotropin-Releasing Hormone (GnRH) receptor
antagonist, elagolix, in patients with endometriosis. Consistent
with previously reported six month (Petal Study) and three month
(Lilac Petal Study) results, a favorable safety profile and
clinically meaningful efficacy have again been confirmed through
month six of the Lilac Petal Study. This newly available data also
provides clinical confirmation of Neurocrine's extensive
pharmacologic modeling related to the elagolix dose-response
continuum. The outcome of primary interest at month six was the
impact of the elagolix 250 mg dose on bone mineral density (BMD) as
measured by dual energy X-ray absorptiometry (DXA) scanning.
Over the six month treatment period, elagolix 150 mg once daily
had minimal impact on BMD (-0.80% mean change from baseline, femur;
-0.66% mean change from baseline, spine). The 250 mg once daily
dose, as expected, had slightly greater percentage change from
baseline at month six (-1.0% femur, -1.6% spine). The 150 mg once
daily BMD profile in this Lilac Petal Study is consistent with that
previously demonstrated in the six-month Petal Study.
"We selected the 150 mg and 250 mg once daily doses for this
study based upon predictions generated from extensive modeling of
dose, estradiol and bone mineral density relationships. Prior to
this study we anticipated that the 250 mg dose would provide
exposure such that we would start to see an increased impact on
bone mineral density in a small portion of study subjects. The
Lilac Petal data confirm that our modeling of the dose-response
curve was accurate," said Chris O'Brien, Chief Medical Officer of
Neurocrine Biosciences, "Most importantly, we find that the 250 mg
once-daily dose, chosen to inform us about the upper limit of
dosing, met the pre-defined threshold for bone impact."
From an efficacy standpoint, the exploratory daily pain scales
for Dysmenorrhea and Non-Menstrual Pelvic Pain demonstrated that
women had minimal endometriosis pain symptoms at month six (mean
scores of approximately 0.5 for both doses and both of the 0-3
scales). The overall assessment of benefit using the Patient Global
Impression of Change (PGIC) revealed that 80% of elagolix 150 mg
subjects and 79% of elagolix 250 mg subjects were "Much Improved"
or "Very Much Improved" after six months of treatment. Subjects
treated with elagolix also reported considerable improvement on the
Endometriosis Health Profile (EHP-5), a validated
endometriosis-specific scale which reveals the impact of treatment
on a variety of health outcome domains. The core pain dimension of
the EHP-5 documented the marked improvement of
endometriosis-related pain and its impact on daily function for
both doses of elagolix. The symptom improvement demonstrated by all
of the efficacy assessments was maintained over the entire study
duration and consistent with results across the entire Phase II
program.
Dr. O'Brien also commented, "The magnitude of improvement and
the related responder rates across the numerous efficacy scales
were similar for both the 150 mg and 250 mg doses of elagolix and,
given the superior bone safety profile, the 150 mg once daily dose
appears to be the optimal choice for upcoming Phase III
trials."
There were no signals of dose limiting adverse events or changes
in clinical chemistry, hematology, urinalysis and ECG testing
evident for either dose of elagolix; treatment over six months was
generally safe and well tolerated. Discontinuation due to adverse
events was 2.9% for 150 mg, 5.6% for 250 mg. Adverse Events
reported by the 150 mg and 250 mg groups included nausea (8.7% and
8.3% respectively) and headache (8.7% and 5.6%), both consistent
with prior trials. There were no drug-related Serious Adverse
Events. After six months of treatment, the median values for serum
estradiol were 41 pg/ml (150 mg) and 21 pg/ml (250 mg) in keeping
with the dose-response modeling.
The Lilac Petal Study included six months of treatment; the
initial three months randomized 155 subjects to one of three dosing
arms (placebo, 150mg elagolix once daily, 250mg elagolix once
daily). The primary endpoint (efficacy evaluation of elagolix vs.
placebo) was previously reported at the conclusion of the month
three placebo-controlled phase. A total of 125 subjects continued
into the second three months of the trial; 38 subjects were
re-randomized from their initial assignment of placebo to elagolix
150 mg (n=18) or elagolix 250 mg (n=20) once daily in a
double-blind fashion. Those subjects who were initially randomized
to elagolix continued under double-blind conditions.
Neurocrine will discuss these clinical trial results as part of
its second quarter earnings call scheduled for July 30, 2009 at
8:30 a.m. Eastern Daylight Time (5:30 a.m. Pacific Daylight Time).
Particpants can access the live conference by dialing
1-800-895-0198 (US) or 785-424-1053 (International) using the
conference passcode 7NEURO. The call can also be accessed via the
webcast through the Company's website at http://www.neurocrine.com/.
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 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 and report on Form 10-Q for the quarter ended March 31, 2009.
Neurocrine undertakes no obligation to update the statements
contained in this press release after the date hereof.
Source: Neurocrine Biosciences, Inc.
CONTACT: Neurocrine Biosciences, Investor Relations,
+1-858-617-7600
Web Site: http://www.neurocrine.com/
Posted: July 2009
