Galcanezumab-Gnlm

1 INDICATIONS AND USAGE EMGALITY ® is a calcitonin-gene related peptide antagonist indicated in adults for the: preventive treatment of migraine. ( 1.1 ) treatment of episodic cluster headache. ( 1.2 ) 1.1 Migraine EMGALITY is indicated for the preventive treatment of migraine in adults. 1.2 Episodic Cluster Headache EMGALITY is indicated for the treatment of episodic cluster headache in adults.

2 DOSAGE AND ADMINISTRATION For subcutaneous use only. ( 2.1 , 2.2 , 2.3 ) Migraine recommended dosage: 240 mg loading dose (administered as two consecutive injections of 120 mg each), followed by monthly doses of 120 mg. ( 2.1 ) Episodic cluster headache recommended dosage: 300 mg (administered as three consecutive injections of 100 mg each) at the onset of the cluster period, and then monthly until the end of the cluster period. ( 2.2 ) Administer in the abdomen, thigh, back of the upper arm, or buttocks subcutaneously. ( 2.3 ) 2.1 Recommended Dosing for Migraine The recommended dosage of EMGALITY is 240 mg (two consecutive subcutaneous injections of 120 mg each) once as a loading dose, followed by monthly doses of 120 mg injected subcutaneously. If a dose of EMGALITY is missed, administer as soon as possible. Thereafter, EMGALITY can be scheduled monthly from the date of the last dose. 2.2 Recommended Dosing for Episodic Cluster Headache The recommended dosage of EMGALITY is 300 mg (three consecutive subcutaneous injections of 100 mg each) at the onset of the cluster period, and then monthly until the end of the cluster period. If a dose of EMGALITY is missed during a cluster period, administer as soon as possible. Thereafter, EMGALITY can be scheduled monthly from the date of the last dose until the end of the cluster period. 2.3 Important Administration Instructions EMGALITY is for subcutaneous use only. EMGALITY is intended for patient self-administration. Prior to use, provide proper training to patients and/or caregivers on how to prepare and administer EMGALITY using the single-dose prefilled pen or single-dose prefilled syringe, including aseptic technique [see How Supplied/Storage and Handling ( 16.2 ) and Instructions for Use] : Protect EMGALITY from direct sunlight. Prior to subcutaneous administration, allow EMGALITY to sit at room temperature for 30 minutes. Do not warm by using a heat source such as hot water or a microwave. Do not shake the product. Inspect EMGALITY visually for particulate matter and discoloration prior to administration, whenever solution and container permit [see Dosage Forms and Strengths ( 3 ) and How Supplied/Storage and Handling ( 16.1 )] . Do not use EMGALITY if it is cloudy or there are visible particles. Administer EMGALITY in the abdomen, thigh, back of the upper arm, or buttocks subcutaneously. Do not inject into areas where the skin is tender, bruised, red, or hard. Both the prefilled pen and prefilled syringe are single-dose and deliver the entire contents.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] Hypertension [see Warnings and Precautions ( 5.2 )] Raynaud's Phenomenon [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (incidence ≥2% and at least 2% greater than placebo) in EMGALITY clinical studies were injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 with rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. Migraine The safety of EMGALITY has been evaluated in 2586 patients with migraine who received at least one dose of EMGALITY, representing 1487 patient-years of exposure. Of these, 1920 patients were exposed to EMGALITY once monthly for at least 6 months, and 526 patients were exposed for 12 months. In placebo-controlled clinical studies (Studies 1, 2, and 3), 705 patients received at least one dose of EMGALITY 120 mg once monthly, and 1451 patients received placebo, during 3 months or 6 months of double-blind treatment [see Clinical Studies ( 14.1 )] . Of the EMGALITY-treated patients, approximately 85% were female, 77% were white, and the mean age was 41 years at study entry. The most common adverse reaction was injection site reactions. In Studies 1, 2, and 3, 1.8% of patients discontinued double-blind treatment because of adverse events. Table 1 summarizes the adverse reactions that occurred within up to 6 months of treatment in the migraine studies. Table 1: Adverse Reactions Occurring in Adults with Migraine with an Incidence of at least 2% for EMGALITY and at least 2% Greater than Placebo (up to 6 Months of Treatment) in Studies 1, 2, and 3 a Injection site reactions include multiple related adverse event terms, such as injection site pain, injection site reaction, injection site erythema, and injection site pruritus. Adverse Reaction EMGALITY 120 mg Monthly (N=705) % Placebo Monthly (N=1451) % Injection site reactions a 18 13 Episodic Cluster Headache EMGALITY was studied for up to 2 months in a placebo-controlled trial in patients with episodic cluster headache (Study 4) [see Clinical Studies ( 14.2 )] . A total of 106 patients were studied (49 on EMGALITY and 57 on placebo). Of the EMGALITY-treated patients, approximately 84% were male, 88% were white, and the mean age was 47 years at study entry. Two EMGALITY-treated patients discontinued double-blind treatment because of adverse events. Overall, the safety profile observed in patients with episodic cluster headache treated with EMGALITY 300 mg monthly is consistent with the safety profile in migraine patients. 6.2 Immunogenicity As with all therapeutic proteins, 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. For these reasons, comparison of the incidence of antibodies to galcanezumab-gnlm in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. The immunogenicity of EMGALITY has been evaluated using an in vitro immunoassay for the detection of binding anti-galcanezumab-gnlm antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro ligand-binding immunoassay was performed to detect neutralizing antibodies. In controlled studies with EMGALITY up to 6 months (Study 1, Study 2, and Study 3), the incidence of anti-galcanezumab-gnlm antibody development was 4.8% (33/688) in patients receiving EMGALITY once monthly (32 out of 33 of whom had in vitro neutralizing activity). With 12 months of treatment in an open-label study, up to 12.5% (16/128) of EMGALITY-treated patients developed anti-galcanezumab-gnlm antibodies, most of whom tested positive for neutralizing antibodies. Although anti-galcanezumab-gnlm antibody development was not found to affect the pharmacokinetics, safety or efficacy of EMGALITY in these patients, the available data are too limited to make definitive conclusions. 6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of EMGALITY. 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 EMGALITY exposure. Immune System Disorders — Anaphylaxis, angioedema [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] . Skin and Subcutaneous Tissue Disorders — Rash. Vascular Disorders — Hypertension [see Warnings and Precautions ( 5.2 )] , Raynaud's Phenomenon [see Warnings and Precautions ( 5.3 )]

12.3 Pharmacokinetics Galcanezumab-gnlm exhibits linear pharmacokinetics and exposure increases proportionally with doses between 1 and 600 mg. A loading dose of 240 mg achieved the serum galcanezumab-gnlm steady-state concentration after the first dose. A dose of 300 mg monthly would achieve steady-state concentration after the fourth dose. The time to maximum concentration is 5 days, and the elimination half-life is 27 days. There was no difference in pharmacokinetic parameters between healthy volunteers, patients with episodic or chronic migraine, and patients with episodic cluster headache. Absorption Following a subcutaneous dose of galcanezumab-gnlm, the time to maximum concentration was about 5 days. Injection site location did not significantly influence the absorption of galcanezumab-gnlm. Distribution The apparent volume of distribution (V/F) of galcanezumab-gnlm was 7.3 L (34% Inter Individual Variability [IIV]). Metabolism and Elimination Galcanezumab-gnlm is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG. The apparent clearance (CL/F) of galcanezumab-gnlm was 0.008 L/h and the elimination half-life of galcanezumab was approximately 27 days. Specific Populations Age, Sex, Weight, Race, Ethnicity The pharmacokinetics of galcanezumab-gnlm were not affected by age, sex, race, subtypes of migraine spectrum (episodic or chronic migraine), or headache diagnosis (migraine vs. episodic cluster headache) based on a population pharmacokinetics analysis. Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab-gnlm. Patients with Renal or Hepatic Impairment Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab-gnlm. Population pharmacokinetic analysis of integrated data from the galcanezumab-gnlm clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab-gnlm in patients with mild or moderate renal impairment. Patients with severe renal impairment (creatinine clearance <30 mL/min) have not been studied. Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab-gnlm. No dedicated clinical studies were conducted to evaluate the effect of hepatic impairment or renal impairment on the pharmacokinetics of galcanezumab-gnlm. Drug Interaction Studies P450 Enzymes Galcanezumab-gnlm is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.