Less than 2-fold accumulation was observed in trough serum concentrations (Cmin) for episodic and chronicmigraine patients following subcutaneous administration of 70 mg once monthly and 140 mg once monthly

doses (see Table 2). Serum trough concentrations approached steady state by 3 months of dosing. The effectivehalf-life of erenumab-aooe is 28 days.

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Table 2: Pharmacokinetic Parameters of AIMOVIG

AIMOVIG 70 mg

Subcutaneously Once Monthly

AIMOVIG 140 mg

Subcutaneously Once Monthly

Cmax mean (SD)a,b 6.1 (2.1) mcg/mL 15.8 (4.8) mcg/mL

AUClast mean (SD)a,b 159 (58) day*mcg/mL 505 (139) day*mcg/mL

Cmin (SD)

Episodic migraine 5.7 (3.1) mcg/mL 12.8 (6.5) mcg/mL

Chronic migraine 6.2 (2.9) mcg/mL 14.9 (6.5) mcg/mL a SD = standard deviation

b from a single-dose study

Absorption

Following a single subcutaneous dose of 70 mg or 140 mg erenumab-aooe administered to healthy adults,median peak serum concentrations were attained in approximately 6 days, and estimated absolute bioavailability

was 82%.

Distribution

Following a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase(Vz) was estimated to be 3.86 (0.77) L.

Metabolism and Excretion

Two elimination phases were observed for erenumab-aooe. At low concentrations, the elimination ispredominantly through saturable binding to target (CGRP receptor), while at higher concentrations the

elimination of erenumab-aooe is largely through a non-specific, non-saturable proteolytic pathway.

Specific Populations

The pharmacokinetics of erenumab-aooe were not affected by age, gender, race, or subtypes of migrainespectrum (episodic or chronic migraine) based on population pharmacokinetics analysis.

Patients with Renal or Hepatic Impairment

Population pharmacokinetic analysis of integrated data from the AIMOVIG clinical studies did not reveal adifference in the pharmacokinetics of erenumab-aooe in patients with mild or moderate renal impairment

relative to those with normal renal function. Patients with severe renal impairment (eGFR< 30 mL/min/1.73 m2) have not been studied. 

No dedicated clinical studies were conducted to eva luate theeffect of hepatic impairment or renal impairment on the pharmacokinetics of erenumab-aooe. Renal or hepaticimpairment is not expected to affect pharmacokinetics of erenumab-aooe.

Drug Interaction StudiesP450 Enzymes Erenumab-aooe is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitantmedications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Oral ContraceptivesIn an open-label drug interaction study in healthy female volunteers, erenumab-aooe (140 mg subcutaneous,single-dose) did not affect the pharmacokinetics of a combined oral contraceptive containing ethinyl estradioland norgestimate.

SumatriptanIn a study in healthy volunteers, concomitant administration of erenumab-aooe with sumatriptan had no effecton the pharmacokinetics of sumatriptan [see Clinical Pharmacology (12.2)].

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13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis