General Information

Eligard (leuprolide acetate) is a gonadotropin releasing hormone (GnRH) agonist.

Eligard is specifically indicated for the palliative treatment of advanced prostate cancer.

Eligard is supplied as an injection for subcutaneous administration. Eligard provides continuous release of leuprolide acetate over a one-, three-, four-, or six-month treatment period. See the table below. The injection delivers the dose of leuprolide acetate incorporated in a polymer formulation.

Mechanism of Action

Leuprolide acetate, an LH-RH agonist, acts as a potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses. Animal and human studies indicate that after an initial stimulation, chronic administration of leuprolide acetate results in suppression of ovarian and testicular steroidogenesis. This effect is reversible upon discontinuation of drug therapy.

In humans, administration of leuprolide acetate results in an initial increase in circulating levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in premenopausal females). However, continuous administration of leuprolide acetate results in decreased levels of LH and FSH. In males, testosterone is reduced to below castrate threshold. These decreases occur within two to four weeks after initiation of treatment. Long-term studies have shown that continuation of therapy with leuprolide acetate maintains testosterone below the castrate level for up to seven years. (from Eligard FDA Label)

Side Effects

Adverse events associated with the use of Eligard may include (but are not limited to) the following:

• Malaise
• Fatigue
• Dizziness
• Hot flashes/sweats
• Gastroenteritis
• Colitis

Clinical Trial Results

One open-label, multicenter study was conducted with each Eligard formulation (7.5 mg, 22.5 mg, 30 mg, and 45 mg) in patients with Jewett stage A though D prostate cancer who were treated with at least a single injection of study drug. These studies evaluated the achievement and maintenance of castrate serum testosterone suppression over the duration of therapy. During the AGL9904 study using Eligard 7.5 mg, once testosterone suppression was achieved, no patients (0%) demonstrated breakthrough (concentration > 50 ng/dL) at any time in the study. During the AGL9909 study using Eligard 22.5 mg, once testosterone suppression was achieved, only one patient (< 1%) demonstrated breakthrough following the initial injection; that patient remained below the castrate threshold following the second injection. During the AGL0001 study using Eligard 30 mg, once testosterone suppression was achieved, three patients (3%) demonstrated breakthrough. In the first of these patients, a single serum testosterone concentration of 53 ng/dL was reported on the day after the second injection. In this patient, castrate suppression was reported for all other time points. In the second patient, a serum testosterone concentration of 66 ng/dL was reported immediately prior to the second injection. This rose to a maximum concentration of 147 ng/dL on the second day after the second injection. In this patient, castrate suppression was again reached on the seventh day after the second injection and was maintained thereafter. In the final patient, serum testosterone concentrations > 50 ng/dL were reported at 2 and at 8 hours after the second injection. Serum testosterone concentration rose to a maximum of 110 ng/dL on the third day after the second injection. In this patient, castrate suppression was again reached eighteen days after the second injection and was maintained until the final day of the study, when a single serum testosterone concentration of 55 ng/dL was reported. During the AGL0205 study using Eligard 45 mg, once testosterone suppression was achieved, one patient (<1%) demonstrated breakthrough. This patient reached castrate suppression at Day 21 and remained suppressed until Day 308 when his testosterone level rose to 112 ng/dL. At Month 12 (Day 336), his testosterone was 210 ng/dL.