FDA just approved th first gonsdotropin-releasing hormone (GnRH) drug for the treatment of Advanced Prostate Cancer. This newly approved gonadotropin-releasing hormone (GnRH) receptor antagonist demonstrates rapid, long-term suppression of testosterone.
Ferring Pharmaceuticals, USA (FP) received approval from the U.S. Food and Drug Administration (FDA) for degarelix, (generic name) which is a new injectable gonadotropin-releasing hormone (GnRH) receptor antagonist used for the treatment of advanced prostate cancer. At this time the FDA is still working with PFP to develop a trade name. Assoon as a name has been decided FP says that it will immediately begin commercialization of the new drug. The Committee for Medicinal Products for Human Use (CHMP), part of the European Medicines Agency (EMEA), has also recommended granting a marketing authorization for degarelix in Europe .
In the phase III studies degarelix demonstrated that it is at least as effective as leuprolide (Lupron Depot(R)) in sustaining castrate levels or lower of testosterone, and had a statistically significant faster reduction of testosterone. At Day 3 of treatment, 96% of degarelix patients achieved castrate levels of testosterone, compared with zero percent receiving leuprolide. By Day 14, 99% of degarelix patients achieved castrate levels of testosterone, compared with 18% receiving leuprolide.
Prostate Specific Antigen (PSA) levels were also monitored as a secondary endpoint in the trial. PSA levels were lowered by 64% two weeks after administration of degarelix, 85% after one month, 95% after three months, and remained suppressed throughout the one year of treatment. There has not been any evidence that the speed of PSA decline provides any clinical or survival benefit.
Degarelix is the only GnRH receptor antagonist approved by the FDA for the treatment of hormonally-sensitive advanced prostate cancer. Although the commonly used GnRH receptor antagonists that are used are successful in reducing testosterone levels in men with advanced prostate cancer they have not been approved for advanced prostate cancer. These other drugs are actually used off label.
Degarelix works differently than LHRH agonists, specifically by binding reversibly to GnRH receptors on cells in the pituitary gland, quickly reducing the release of gonadotropins and consequently testosterone.
“Use of a GnRH receptor antagonist is a highly efficient way to stop the production of testosterone,” said Neal Shore, MD, FACS, Medical Director for Carolina Urologic Research Center, a clinical trial investigator and advisor to Ferring. “The approval of degarelix offers the medical community an effective alternative in the treatment of hormonally-sensitive prostate cancer. Now prostate cancer can be treated with immediate inhibition of the GnRH receptors, inducing rapid reduction of testosterone to castrate levels, and sustaining those levels over time, which are the goals of systemic therapy. When a patient has disease recurrence, it is always encouraging to clinicians and patients to see PSA levels fall so rapidly.”
Phase III Study Results
The 12-month, randomized, open-label, parallel-group Phase III study evaluated the efficacy and safety of degarelix compared with leuprolide administered monthly over one year of prostate cancer treatment. Patients with histologically confirmed prostate cancer were randomized to either degarelix or leuprolide: a degarelix subcutaneous (under the skin) injection of 240 mg for one month with monthly maintenance doses of 80 mg (n=207) or monthly intermuscular (into the muscle) injections of leuprolide depot 7.5 mg (n=201).
The primary endpoint was testosterone suppression to less than or equal to 50 ng/dL during monthly measurements from Day 28 to Day 364. Degarelix was at least as effective as leuprolide in achieving and maintaining castrate levels of testosterone.
N Patients with % (95% CI)
Degarelix 207 202 97.2
Leuprolide 7.5 mg 201 194 96.4
Suppression of testosterone levels to less than or equal to 50 ng/dL occurred significantly faster in patients receiving degarelix than in those receiving leuprolide. At Day 3, 96% of patients demonstrated treatment response. In that same time period, none of the patients who received leuprolide demonstrated treatment response. Conversely, testosterone levels had increased by a median of 65% in 80% of those receiving leuprolide at Day 3.
Overall, the most commonly observed adverse reactions during degarelix therapy included injection site reactions (e.g. pain, erythema, swelling or induration), hot flushes, increased weight, fatigue, and increases in serum levels of transaminases and gamma-glutamyltransferase (GGT). 99% of these observed adverse reactions were Grade 1 or 2 (mild to moderate). Specifically relating to the injection site adverse reactions, most were transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (<1%). Grade 3 (severe) injection site reactions occurred in 2% or less of patients receiving degarelix.Well, finally a drug approved for advanced prostate cancer. However, it is not clear other than the quicker response that degarelix provides any new additional benefits in our fight. Although many physicians set the goal for castration at 50 ng/dl, for many men this is not a low enough level for good cancer control. It will be very informative over time to see if degarelix can get men's testosterone level to the better goal of under 20 ng/dl.We also need to see if degarelix might not be effective once the more traditional GnRh drugs have stopped working. Since degarelix operates differently than the other GnRh drugs it might serve as a new second line treatment option.Herb on the Prostate Pointers Mailing List has also raised two excellent questions. He asked about the cost of degarelix as opposed to the cost of Lupron and if degarelix, like lupron, could be use on an intermittent schedule.See Pub Med, a service of the US National Library of Medicine, at www.pubmed.gov and search on Pub Med ID 19035858Joel T Nowak MA, MSW