Neurocrine Biosciences Announces Positive Phase I Results With Its Proprietary, Orally Active GnRH Receptor Antagonist
Tuesday June 24, 7:30 am ET
[As no-one else wants to paste it, I will do it. It is good to have here, once the Yahoo PR has fallen off its cliff. I suppose the folks at Neurocrine can say "So far - so good", but not much more that that. Or is it possible to draw any more far-reaching conclusions from the reported results and the fact that they felt it worthy of a press release?]
SAN DIEGO, June 24 /PRNewswire-FirstCall/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX - News) announced today positive results from the Company's Phase I clinical trial with its proprietary, orally active small molecule Gonadotropin-Releasing Hormone (GnRH) receptor antagonist to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple dosing of NBI-42902 in healthy pre-menopausal women. Results demonstrated that NBI-42902 was safe and well tolerated.
Eighteen healthy pre-menopausal women participated in this randomized, double-blind, placebo-controlled, parallel group, multiple-dose regimen study. The subjects were assigned to three groups of six with each subject receiving daily doses of either placebo, 75 mg of NBI-42902 once a day or 37.5 mg of NBI-42902 twice a day for seven consecutive days.
Preliminary pharmacokinetic data demonstrated that NBI-42902 was absorbed rapidly after oral administration. The systemic exposure as measured by AUC and Cmax was proportional to the total dose given either once-a-day or twice-a-day and was similar between Day One and Day Seven of dosing indicating no evidence of accumulation, enzyme induction or inhibition. Initial pharmacodynamic evaluation indicated suppression of luteinizing hormone (LH) and follicle stimulating hormone (FSH) as expected based on data from a previous study with the compound in post-menopausal women. Furthermore, gonadal suppression was achieved resulting in suppression of estrogen to levels anticipated to be therapeutic. NBI-42902 was well tolerated by all subjects with no discontinuations or serious adverse events. These results indicate that an orally active GnRH antagonist may be useful in suppression of estrogen levels in the treatment of hormone dependent diseases in pre-menopausal women.
GnRH is a neuroendocrine peptide which stimulates the secretion of the pituitary LH, which in turn stimulates the production of estrogen by the ovary or testosterone by the testis. The most widely prescribed drugs modulating at the GnRH receptor are peptide agonists such as Lupron® and Zoladex® with estimated combined sales in excess of $2.5 billion worldwide. These compounds are administered as injectable depots which act by first stimulating then eventually inhibiting the secretion of pituitary LH and consequently, estrogen or testosterone production. These drugs have proven clinically useful in treating hormone dependent diseases such as endometriosis, uterine fibroids, prostate cancer and breast cancer, as well as being used for assisted- reproductive therapy. NBI-42902 discovered and developed within Neurocrine, is a specific highly potent non-peptide, orally active antagonist of the GnRH receptor. This compound inhibits pituitary LH secretion directly, potentially preventing the several week delay and flare associated with agonist therapy. Neurocrine believes that orally active, non-peptide GnRH antagonists should provide a more rapid onset of action, increased dosing flexibility and greater patient acceptability over currently available treatments. |
