FIRMAGON SIDE EFFECTS

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

FIRMAGON was studied in a randomized, open-label trial in which patients with prostate cancer were randomized to receive FIRMAGON (subcutaneous) or leuprolide (intramuscular) monthly for 12 months.

The most common adverse reactions (≥10%) during FIRMAGON therapy are injection site reactions (e.g., pain, erythema, swelling or induration), hot flashes, and increases in serum levels of transaminases and gammaglutamyltransferase (GGT). The majority of the adverse reactions were Grade 1 or 2, with Grade 3/4 adverse reaction incidences of 1% or less.

Adverse reactions reported in ≥ 5% of patients treated with FIRMAGON (subcutaneous) 240 mg starting dose and then 80 mg maintenance dose once every 28 days or who were treated with 7.5 mg of leuprolide (intramuscular) every 28 days are shown in Table1.

Table 1: Adverse Reactions Reported in ≥ 5% of Patients

The following adverse reactions occurred in 1 to < 5% of patients treated with FIRMAGON:

Body as a whole: Asthenia, fatigue, fever, night sweats

Digestive system: Nausea

Nervous system: Dizziness, headache, insomnia

The following adverse reactions, not already listed, occurred in ≥ 1% of patients treated in any study with FIRMAGON:

Reproductive System: Erectile dysfunction, testicular atrophy

Endocrine Disorders: Gynecomastia

General: Hyperhidrosis

Gastrointestinal: Diarrhea

Injection Site Reactions

The most frequently reported adverse reactions at the injection sites were pain (28%), erythema (17%), swelling (6%), induration (4%) and nodule (3%). These adverse reactions were mostly transient, of mild to moderate intensity, occurred primarily with the starting dose and led to few discontinuations (<1%). Grade 3 injection site reactions occurred in 2% or less of patients receiving FIRMAGON.

Hepatic Laboratory Abnormalities

Hepatic laboratory abnormalities were primarily Grade 1 or 2 and were generally reversible. Grade 3 hepatic laboratory abnormalities occurred in less than 1% of patients.

FIRMAGON Extension Study

The safety of FIRMAGON administered once every 28 days was evaluated further in an extension study (NCT00451958) in 385 patients who completed the above active-controlled trial. Of the 385 patients, 251 patients continued treatment with FIRMAGON and 135 patients crossed over treatment from leuprolide to FIRMAGON.

The median treatment duration on the extension study was approximately 43 months (range 1 to 58 months). The most common adverse reactions reported in ≥10% of the patients were injection site reactions (e.g., pain, erythema, swelling, induration or inflammation), pyrexia, hot flush, weight loss or gain, fatigue, increases in serum levels of hepatic transaminases and GGT. One percent of patients had injection site infections including abscess. Hepatic laboratory abnormalities in the extension study included the following: Grade 1/2 elevations in hepatic transaminases occurred in 47% of patients and Grade 3 elevations occurred in 1% of patients.

Immunogenicity

As with all peptides, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

Anti-Degarelix Antibodies

Anti-degarelix antibody development has been observed in 10% of patients after treatment with FIRMAGON for 1 year. There is no indication that the efficacy or safety of FIRMAGON treatment is affected by antibody formation.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of FIRMAGON. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Changes In Bone Density

Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with a GnRH agonist. It can be anticipated that long periods of medical castration in men will result in decreased bone density.