ERENUMAB: 1,183 Adverse Event Reports & Safety Profile

Erenumab-aooe is a human immunoglobulin G2 (IgG2) monoclonal antibody that has high affinity binding to the calcitonin gene-related peptide receptor. Erenumab-aooe is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. It is composed of 2 heavy chains, each containing 456 amino acids, and 2 light chains of the lambda subclass, each containing 216 amino acids, with an approximate molecular weight of 150 kDa. AIMOVIG (erenumab-aooe) injection is supplied as a sterile, preservative-free, clear to opalescent, colorless to light yellow solution for subcutaneous administration.

Each

1 mL 70 mg single-dose prefilled autoinjector and 70 mg single-dose prefilled glass syringe contains 70 mg erenumab-aooe, acetate (1.5 mg), polysorbate 80 (0.10 mg), and sucrose (73 mg).

Each

1 mL 140 mg single-dose prefilled autoinjector and 140 mg single-dose prefilled glass syringe contains 140 mg erenumab-aooe, acetate (2.0 mg), polysorbate 80 (0.10 mg), and sucrose (65 mg). Enclosed within the autoinjector is a single-dose, prefilled glass syringe. The solution of AIMOVIG has a pH of 5.2.

AND USAGE AIMOVIG is indicated for the preventive treatment of migraine in adults. AIMOVIG is a calcitonin gene-related peptide receptor antagonist indicated for the preventive treatment of migraine in adults. ( 1 )

AND ADMINISTRATION For subcutaneous use only ( 2.1 , 2.2 ) Recommended dosage is 70 mg once monthly; some patients may benefit from a dosage of 140 mg once monthly ( 2.1 ) Administer in the abdomen, thigh, or upper arm subcutaneously ( 2.2 )

See

Dosage and Administration for important administration instructions ( 2.2 )

2.1 Recommended Dosing The recommended dosage of AIMOVIG is 70 mg injected subcutaneously once monthly. Some patients may benefit from a dosage of 140 mg injected subcutaneously once monthly. If a dose of AIMOVIG is missed, administer as soon as possible. Thereafter, AIMOVIG can be scheduled monthly from the date of the last dose.

2.2 Important Administration Instructions AIMOVIG is for subcutaneous use only. AIMOVIG is intended for patient self-administration. Prior to use, provide proper training to patients and/or caregivers on how to prepare and administer AIMOVIG using the single-dose prefilled autoinjector or single-dose prefilled syringe, including aseptic technique <span class="opacity-50 text-xs">[see Instructions for Use]</span> : Prior to subcutaneous administration, allow AIMOVIG to sit at room temperature for at least 30 minutes protected from direct sunlight <span class="opacity-50 text-xs">[see How Supplied/Storage and Handling (16.2) ]</span>. This is important for administering the entire dose and helps minimize discomfort. Do not warm by using a heat source such as hot water or a microwave. Do not shake the product. Inspect visually for particulate matter and discoloration prior to administration <span class="opacity-50 text-xs">[see Dosage Forms and Strengths (3) ]</span> . Do not use if the solution is cloudy or discolored or contains flakes or particles. Administer AIMOVIG in the abdomen, thigh, or upper arm subcutaneously. Do not inject into areas where the skin is tender, bruised, red, or hard. Both prefilled autoinjector and prefilled syringe are single-dose and deliver the entire contents.

AIMOVIG is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.1) ] . AIMOVIG is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients. ( 4 )

REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Constipation with Serious Complications [see Warnings and Precautions (5.2) ] Hypertension [see Warnings and Precautions (5.3) ] Raynaud's Phenomenon [see Warnings and Precautions (5.4) ] The most common adverse reactions in AIMOVIG clinical studies (occurring in at least 3% of treated patients and more often than placebo) are injection site reactions and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-77-AMGEN (1-800-772-6436) 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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of AIMOVIG has been evaluated in 2537 patients with migraine who received at least one dose of AIMOVIG, representing 3040.2 patient-years of exposure. Of these, 2271 patients were exposed to 70 mg or 140 mg once monthly for at least 6 months, 1305 patients were exposed for at least 12 months, and 216 patients were exposed through 5 years. In placebo-controlled clinical studies (Studies 1, 2, and 3) of 2184 patients, 787 patients received at least one dose of AIMOVIG 70 mg once monthly, 507 patients received at least one dose of AIMOVIG 140 mg once monthly, and 890 patients received placebo during 3 months or 6 months of double-blind treatment <span class="opacity-50 text-xs">[see Clinical Studies (14) ]</span> .

Approximately

84% were female, 91% were white, and the mean age was 42 years at study entry. The most common adverse reactions (incidence ≥ 3% and more often than placebo) in the migraine studies were injection site reactions and constipation.

Table

1 summarizes the adverse reactions that occurred during the first 3 months in the migraine studies (Studies 1, 2, and 3).

Table

1: Adverse Reactions Occurring with an Incidence of at Least 2% for Either Dose of AIMOVIG and at Least 2% Greater than Placebo During the First 3 Months in Studies 1, 2, and 3 Adverse Reaction AIMOVIG 70 mg Once Monthly N = 787 % AIMOVIG 140 mg Once Monthly N = 507 % Placebo N = 890 % Injection site reactions Injection site reactions include multiple adverse reactions related terms, such as injection site pain and injection site erythema. , The rate of injection site reactions reported in Table 1 is with the prefilled syringe. 6 5 3 Constipation 1 3 1 Cramps, muscle spasms < 1 2 < 1 In Studies 1, 2, and 3, 1.3% of patients treated with AIMOVIG 70 mg or 140 mg discontinued double-blind treatment because of adverse events. The most frequent injection site reactions were injection site pain, injection site erythema, and injection site pruritus.

6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of AIMOVIG. 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.

Immune System

Disorders: Hypersensitivity reactions, including rash, angioedema, and anaphylaxis [see Warnings and Precautions (5.1) ].

Gastrointestinal

Disorders: Constipation with serious complications [see Warnings and Precautions (5.2) ] , oral mucosal ulceration . Skin and Subcutaneous Tissue Disorders: Rash, alopecia.

Vascular

Disorders: Hypertension [see Warnings and Precautions (5.3) ] , Raynaud's Phenomenon [see Warnings and Precautions (5.4) ].

AND PRECAUTIONS Hypersensitivity Reactions: If a serious hypersensitivity reaction occurs, discontinue administration of AIMOVIG and initiate appropriate therapy. Hypersensitivity reactions can occur within hours to more than one week after administration. ( 5.1 ) Constipation with Serious Complications: Serious complications of constipation may occur. ( 5.2 ) Hypertension: New-onset or worsening of pre-existing hypertension may occur. ( 5.3 ) Raynaud's Phenomenon: New-onset or worsening of pre-existing Raynaud's phenomenon may occur. ( 5.4 )

5.1 Hypersensitivity Reactions Hypersensitivity reactions, including rash, angioedema, and anaphylaxis, have been reported with AIMOVIG in postmarketing experience. Most hypersensitivity reactions were not serious and occurred within hours of administration, although some occurred more than one week after administration. If a serious or severe hypersensitivity reaction occurs, discontinue administration of AIMOVIG and initiate appropriate therapy <span class="opacity-50 text-xs">[see Contraindications (4) , and Patient Counseling Information (17) ]</span> .

5.2 Constipation with Serious Complications Constipation with serious complications has been reported following the use of AIMOVIG in the postmarketing setting. There were cases that required hospitalization, including cases where surgery was necessary. In a majority of these cases, the onset of constipation was reported after the first dose of AIMOVIG; however, patients have also presented with constipation later on in treatment. AIMOVIG was discontinued in most reported cases of constipation with serious complications. Constipation was one of the most common (up to 3%) adverse reactions reported in clinical studies <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Monitor patients treated with AIMOVIG for severe constipation and manage as clinically appropriate <span class="opacity-50 text-xs">[see Patient Counseling Information (17) ]</span> . The concurrent use of medications associated with decreased gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation-related complications.

5.3 Hypertension Development of hypertension and worsening of pre-existing hypertension have been reported following the use of AIMOVIG in the postmarketing setting. Many of the patients had pre-existing hypertension or risk factors for hypertension. There were cases requiring pharmacological treatment and, in some cases, hospitalization. Hypertension may occur at any time during treatment but was most frequently reported within seven days of dose administration. In the majority of the cases, the onset or worsening of hypertension was reported after the first dose. AIMOVIG was discontinued in many of the reported cases. Monitor patients treated with AIMOVIG for new-onset hypertension, or worsening of pre-existing hypertension, and consider whether discontinuation of AIMOVIG is warranted if evaluation fails to establish an alternative etiology.

5.4 Raynaud&apos;s Phenomenon Development of Raynaud&apos;s phenomenon and recurrence or worsening of pre-existing Raynaud&apos;s phenomenon have been reported in the postmarketing setting following the use of CGRP antagonists, including AIMOVIG. In reported cases with monoclonal antibody CGRP antagonists, symptom onset occurred a median of 71 days following dosing. Many of the cases reported serious outcomes, including hospitalizations and disability, generally related to debilitating pain. In most reported cases, discontinuation of the CGRP antagonist resulted in resolution of symptoms. AIMOVIG should be discontinued if signs or symptoms of Raynaud&apos;s phenomenon develop, and patients should be evaluated by a healthcare provider if symptoms do not resolve. Patients with a history of Raynaud&apos;s phenomenon should be monitored for, and informed about the possibility of, worsening or recurrence of signs and symptoms.