BJ,
Not what you were looking for, but I was looking for the dosing involved in the prostate cancer & endometriosis indications. This took a little digging, but it appears they'll be very similar. As such, aren't the safety concerns that arose in the prostate cancer NDA even more of a concern for endometriosis? I seem to recall stefaan, an OB/GYN guy, calling it a less threatening disease that already has safe and reasonably effective treatments (correct me if I'm misrepresenting you, stefaan). Doubt the FDA will care about some improvement in efficacy if the safety concerns are any worse than existing treatments . . .
OBGYN.NET Publications covers the the 5th International Symposium on GnRH Analogues in Cancer and Human Reproduction
>>INITIAL SAFETY PROFILE AND HORMONAL DOSE-RESPONSE CHARACTERISTICS OF THE PURE GnRH ANTAGONIST, ABARELIX-DEPOT, IN WOMEN WITH ENDOMETRIOSIS
Paul M. Martha, Michelle E. Gray, Marilyn Campion, Bernice Kuca and Marc B. Garnick for the FASTER (First Abarelix-Depot Study for Treating Endometriosis Rapidly) Study Group. PRAECIS PHARMACEUTICALS, INC., Cambridge, MA, USA.
Abarelix-Depot is a sustained release formulation of a potent, pure GnRH antagonist which is totally devoid of the initial stimulatory activity typical of all known GnRH superagonists. Though the superagonists have proven to be useful clinical tools in the management of endometriosis, an inherent drawback to this class of agents has been the requirement that the patient tolerate the unwanted, but unavoidable, initial stimulatory phase before the desired hormonal suppression phase takes effect. Since pure GnRH antagonists lack such stimulatory activity, their use should therefore be associated with more rapid onset of the desired clinical therapeutic benefit when compared to GnRH superagonist therapy. Therefore, we are investigating the initial safety and efficacy of a sustained release formulation of the pure GnRH antagonist Abarelix-Depot in women with endometriosis and its associated pain. In the ongoing first phase of a larger Phase II trial, 40 women (n=8/arm) are randomized to receive Abarelix--Depot at a dose of 30, 60, 90 or 120 mg SC or leuprolide (Lupron Depot 3.75 mg) IM every 4 weeks for 6 months. Preliminary results on the initial safety and hormonal efficacy are now available. After administration of Abarelix-Depot, all women for whom data are currently available (n=10) have experienced rapid reductions (by study days 2-4) in serum levels of LH, FSH and E2 with a total absence of initial hormonal flare. In contrast, all patients receiving leuprolide (n=5) have experienced rapid increases in serum LH, FSH and E2 consistent with the well-known "hormonal flare" which typifies the GnRH superagonists. In the first patient for whom 2-month hormonal data are available, treatment with Abarelix-Depot at 90 mg SC each month has maintained LH at fully suppressed levels (<1 mIU/mL) and E2 below 20 pg/mL from 24 hours after the first dose through study week 8. To date, there have been no reports of clinical adverse events attributable directly to Abarelix-Depot.
Conclusion: Due to its rapidity of action, lack of hormonal flare, subcutaneous route of administration and attractive initial safety profile, Abarelix-Depot may offer substantial therapeutic advantages over conventional use of GnRH superagonists in women with endometriosis.<<
>>Mol Urol 2000 Fall;4(3):275-7
Abarelix Depot, a GnRH antagonist, v LHRH superagonists in prostate cancer: differential effects on follicle-stimulating hormone. Abarelix Depot study group.
Garnick MB, Campion M.
PRAECIS Pharmaceuticals Inc., Cambridge, Massachusetts 02139-1572, USA.Marc,Garnick@praecis.com
Purpose: A Phase II clinical study contrasted the endocrinologic and biochemical efficacy of Abarelix Depot, a gonadotropin-releasing hormone (GnRH) antagonist, with luteinizing hormone releasing-hormone (LHRH) superagonists, with or without additional antiandrogens, in men with prostate cancer. Methods: This study was open-label and treated 242 men. Abarelix Depot 100 mg was administered by intramuscular injection to 209 men, and LHRH, with or without an antiandrogen, was administered to 33 men according to the formulation used. Serum concentrations of follicle-stimulating hormone (FSH) and other hormones were measured at baseline and at specified time points for the first 85 days of the study. Median serum concentrations of FSH at baseline were similar for the two treatment groups. Results: Men treated with LHRH superagonists, with or without an antiandrogen, had a surge in the serum concentration of FSH on day 2 before FSH concentrations started to decline. Men in the Abarelix Depot group had an immediate and sustained decrease in the serum concentration of FSH. Conclusion: Recent data suggest that FSH may be an independent growth factor for prostate cancer. The Abarelix Depot-induced decreased in FSH may have a role in the treatment of men with endocrine- responsive disease or for those men whose disease has escaped from hormone sensitivity.<<
Emphasis mine
Cheers, Tuck |
