FDA Approves Degarelix

FDA Approves Ferring Pharmaceuticals' Degarelix for Treatment of Advanced Prostate Cancer

PARSIPPANY, N.J., December 24, 2008 /PRNewswire/ -- Ferring Pharmaceuticals, USA today received approval from the U.S. Food and Drug Administration (FDA) for degarelix, a new injectable gonadotropin-releasing hormone (GnRH) receptor antagonist, indicated for patients with advanced prostate cancer. Potential trade names are still under review with the FDA. Following issuance of a trade name, Ferring Pharmaceuticals, USA will immediately begin commercialization in the U.S. On December 18, the Committee for Medicinal Products for Human Use (CHMP), part of the European Medicines Agency (EMEA), recommended granting a marketing authorization for degarelix in Europe. Degarelix is awaiting approval in other key global markets. It is a milestone for the company and represents Ferring's first global product launch.

Phase III studies showed that degarelix 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.

In the clinical trial, prostate specific antigen (PSA) levels were also monitored as a secondary endpoint. 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. These PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline is related to a clinical benefit.

Prostate cancer is known to grow in the presence of testosterone. Suppression of testosterone has been a treatment goal for advanced prostate cancer for many years. Surgical castration was the standard method of reducing testosterone from the 1940s until the mid-1980s when the earliest forms of medical castration, luteinizing hormone releasing hormone (LHRH) agonists, were introduced.

Degarelix is the only GnRH receptor antagonist approved by the FDA for the treatment of hormonally-sensitive advanced prostate cancer. Degarelix achieves medical castration 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.

"Degarelix was discovered in San Diego, developed by Ferring Pharmaceuticals in the U.S. and Europe, and in its pivotal Phase III study demonstrated both an immediate onset of action and a profound long-term suppression of testosterone and PSA," commented Dr. Pascal Danglas, Executive Vice President Clinical & Product Development, at Ferring. "We are delighted to deliver a new treatment option for advanced prostate cancer to the medical community. Ferring has a considerable pipeline of urology products in development, and we expect to introduce additional treatment advances in the urology field in the near future."

"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."

Wayne Anderson, President and CEO Ferring Pharmaceuticals, USA added, "We are enthusiastically preparing to enter this therapeutic area of urology. We respect the challenges physicians and patients face in their fight against prostate cancer and hope that we can help them with this new treatment option. This is a big milestone for the U.S. operating unit, and we have been carefully preparing for over two years for this launch."

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)
                                    treatment response

    Degarelix             207              202                  97.2
    240/80 mg

    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. Degarelix is contraindicated in patients with known hypersensitivity to degarelix or to any of the product components. Degarelix is not indicated in women or pediatric patients. Long-term androgen deprivation therapy prolongs the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in patients taking Class IA (e.g. quinidine, procainamide) or Class III (e.g. amiodarone, sotalol) antiarrhythmic medications.

Prostate cancer is the most common cancer, excluding skin cancers, and the second leading cause of cancer death in American men. About one man in six will be diagnosed with prostate cancer during his lifetime, and one in 35 will die of this disease.(1) Prostate cancer develops from cells in the prostate gland that begin to grow out of control. In most cases, prostate cancer grows slowly and can remain undetected throughout a man's life, although it can grow and spread quickly.(2) The four types of standard treatment are: watchful waiting, surgery, radiation therapy, and hormone therapy, also called androgen deprivation therapy (ADT). Degarelix is a new form of hormone therapy that reversibly binds to the GnRH receptors, inhibiting the production of testosterone. By suppressing the production of testosterone, tumor growth is inhibited.(3)

Ferring Pharmaceuticals Inc. is a subsidiary of Ferring Pharmaceuticals, a privately owned, international pharmaceutical company. Ferring Pharmaceuticals offers a line of urology, orthopaedic and infertility products in the U.S. market. They include: EUFLEXXA(R), (1% sodium hyaluronic acid), BRAVELLE(R) (urofollitropin for injection, purified), MENOPUR(R) and REPRONEX(R) (menotropins for injection, USP), Novarel(R) (chorionic gonadotropin for injection, USP), ENDOMETRIN(R) (progesterone) Vaginal Insert, ACTHREL(R) (corticorelin ovine triflutate for injection), PROSED(R) DS (methenamine, phenyl salicylate, methylene blue, benzoic acid, hyoscyamine sulfate), and DESMOPRESSIN.

Ferring Pharmaceuticals specializes in the research, development and commercialization of compounds in general and pediatric endocrinology, urology, orthopaedics, gastroenterology, obstetrics/gynecology and infertility. For complete prescribing information, call 1-888-FERRING (1-888-337-7464) or visit www.FerringUSA.com.

*Lupron Depot(R) (leuprolide acetate for depot suspension) is a registered trademark of TAP Pharmaceuticals Inc.

CONTACT: Tara Fisher, Kovak-Likly Communications, +1-203-762-8833, tfisher@klcpr.com

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