Phase II Study Meets Primary Bone Mineral Density and Secondary Efficacy
Endpoints Company to Host Conference Call and Webcast Wednesday, September 3rd at
8:30 am ET / 5:30 am PT
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,
-- 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
-- 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
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.
Baseline 150mg qd 75mg bid DMPA
Week 4 mean -3.9* -3.7* -3.8*
Week 24 mean -5.5* -5.2* -5.3*
Week 24 mean -1.5* -1.4* -1.7*
Responder Rate 86% 74% 86%
Week 24 mean -1.2* -1.2* -1.1*
Responder Rate 86% 77% 77%
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.|
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