Neurocrine Biosciences, Inc. (Nasdaq: NBIX) announced additional positive safety and efficacy results from its Phase IIb clinical trial known as the Petal Study (603 study) using its proprietary, orally-active non-peptide 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 followed by six months of no treatment. Database lock and unblinding of the full 48 week data set has provided more insight on the clinical benefits and safety profile of elagolix for the treatment of pain associated with endometriosis.
"As expected, elagolix did not induce significant bone loss over the six-month follow up phase of the Petal Study," said Chris O'Brien, MD, Neurocrine's Chief Medical Officer. "Additionally, we are seeing for the first time an oral GnRH antagonist with a rapid and sustained symptom reduction during treatment that also provides a statistically and clinically significant improvement in symptoms which persists after discontinuation of therapy. These are intriguing results and raise the possibility that elagolix treatment may have a disease modifying effect."
Key findings include the following:
Bone Safety: As previously reported, the primary endpoint of the Petal Study, impact on bone mineral density (BMD), was met at Week 24. Neurocrine now has confirmation of a favorable bone safety profile at Week 48 with no cumulative reduction in BMD evident. Mean change from baseline for elagolix 150 mg qd remained at close to 0% at Week 48, with n-telopeptide values remained close to a mean of 10 nM BCE (normal range 6-19 nM BCE for this age group).
Pain reduction: Sustained improvement at Week 48 compared to baseline was demonstrated (p
Quality of Life: The Endometriosis Health Profile (EHP-5) assessed the impact of endometriosis symptoms on five core domains. At baseline, approximately 80% of subjects reported that they suffered difficulties across all domains "sometimes," "often" or "always." After treatment this shifted dramatically such that 60-80% of subjects said "never" or "rarely" to these same EHP-5 questions. Equally notable is the observation that much of this improvement was sustained post-treatment.
Estradiol and Ovulation: The previously reported pharmacodynamic effect of elagolix was confirmed. Median estradiol values were maintained in the low baseline range while on treatment and, most importantly, were not lowered to values that would be associated with hot flashes or clinically significant bone loss. As reported, Week 24 median estradiol was 47 pg/ml for elagolix once daily and 29 pg/ml for elagolix twice daily. At Week 48, the median values for the groups were normal at 80 pg/ml and 84 pg/ml, respectively. The mean time to ovulation post-treatment was 24 days for women who had been randomized to elagolix and >90% of subjects had evidence of ovulation within 4 weeks of stopping. Prolonged suppression of ovulation was documented, even out to Week 48 in the DMPA subjects who also reported frequent spotting and irregular vaginal bleeding.
Safety and Tolerability: Assessment of vital signs, physical examination, electrocardiogram, and clinical laboratory tests did not reveal any safety concerns. Adverse events that were reported were generally mild and transient in nature and not usually associated with study discontinuation. The most common adverse events in this trial were consistent with what we have observed in the other elagolix trials including headache (approximately 20% of subjects reported 1 or more headaches during the 6 months of treatment) and nausea (approximately 15% of subjects reported 1 or more episode of nausea). The most common reason for premature discontinuation from the study was withdrawal of consent (i.e., subject moved, work conflict, etc). Seven subjects withdrew from the study with excessive, prolonged or breakthrough bleeding attributed to DMPA. The reporting of adverse events decreased by 50% in the post treatment period; no pattern of specific safety concerns due to elagolix have been identified. Hot flashes were reported by approximately 40% of subjects during the screening period (mean 0.4 per day) and 40% during the treatment period (mean 0.7 per day). Approximately 25% of subjects reported hot flashes during the post-treatment period (mean 0.4 per day). No pattern of excessive estradiol suppression was detected.
The twelve-month data from the Petal Study will be presented at various upcoming scientific meetings and in manuscript form. The bone data from the Petal Study are scheduled for presentation at the Endocrine Society Meeting in Washington, DC on June 12, 2009. The Petal Study safety and efficacy data have been submitted for the American Society for Reproductive Medicine (ASRM) meeting scheduled this fall in Atlanta. A subset of the Petal Study subjects will return for Week 72 DXA scans and clinical assessments to satisfy earlier arrangements made in consultation with the FDA.
Neurocrine Biosciences, Inc. is a biopharmaceutical company focused on neurological and endocrine related 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.
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 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
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