1 Adverse Reaction Overview Adults Hypersensitivity reactions, including rash, pruritus and urticaria were reported with fremanezumab in less than 1% of patients in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment.
Most reactions were reported from within hours to one month after administration. Hypersensitivity reactions, including urticaria, pruritus, rash and swelling/edema have also been reported with fremanezumab in post-marketing experience.
Very common reported adverse drug reactions (ADRs) from the clinical trials were local reactions at the injection site pain, induration, erythema and pruritus. The adverse reactions that most commonly led to discontinuations were injection site reactions.
Pediatrics No new clinical trial safety findings were noted for AJOVY use in the pediatric population compared to the known safety profile from the adult clinical trials. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.
Therefore, the frequencies of adverse reactions observed in the clinical trials may not reflect frequencies observed in clinical practice and should not be compared to frequencies reported in clinical trials of another drug. The safety of AJOVY was evaluated in 2512 adult patients with migraine who received at least one dose of AJOVY 225 mg monthly or AJOVY 675 mg quarterly for at least six months; 775 patients for at least 12 months; and 138 patients for at least 15 months.
In placebo- controlled clinical trials (Studies 1 and 2), 662 patients received AJOVY 225 mg monthly for 12 weeks (with or without a loading dose of 675 mg), and 663 patients received AJOVY 675 mg quarterly for 12 weeks (See CLINICAL TRIALS) .
In the controlled trials, 87% of patients were female, 80% were White, and the mean age was 41 years. The most common adverse reactions in the clinical trials for the preventive treatment of migraine were injection site reactions. The adverse reactions that most commonly led to discontinuations were injection site reactions.
Patients with significant cardiovascular disease, vascular ischemia, or thrombotic events, such as cerebrovascular accident, transient ischemic attacks, deep vein thrombosis, or pulmonary embolism were excluded from the clinical trials.
(See CLINICAL TRIALS) Table 2: Adverse Reactions Occurring with an Incidence of ≥ 1% and Greater Than Placebo in Episodic and Chronic Migraine Studies System Organ Class Preferred Term AJOVY 225 mg monthly N=290 AJOVY 675 mg quarterly N=667 Placebo N=668 Injection site reactions* 43 % 45 % 38 % *Injection site reactions include multiple related adverse event terms, such as injection site pain, induration, and erythema Table 3: Treatment Emergent adverse events occurring with an incidence of ≥1% in the Placebo Controlled Studies System Organ Class Preferred Term AJOVY 225 mg monthly N=290 n= (%) AJOVY 675 mg quarterly N=667 n= (%) Placebo N=668 n= (%) Patients with at least 1 AE 192 (66) 458 (69) 411 (62) System Organ Class Preferred Term AJOVY 225 mg monthly N=290 n= (%) AJOVY 675 mg quarterly N=667 n= (%) Placebo N=668 n= (%) Gastrointestinal Disorders Nausea 4 (1) 11 (2) 16 (2) Diarrhoea 2 (<1) 5 (<1) 8 (1) General disorders and administration site conditions Injection site pain 87 (30) 200 (30) 180 (27) Injection site induration 71 (24) 131 (20) 113 (17) Injection site erythema 52 (18) 135 (20) 101 (15) Injection site haemorrhage 3 (1) 16 (2) 16 (2) Injection site pruritus 4 (1) 10 (1) 2 (<1) Fatigue 2 (<1) 9 (1) 9 (1) Injection site rash 3 (1) 5 (<1) 0 Injection site swelling 3 (1) 4 (<1) 0 Infections and infestations Upper respiratory tract infection 16 (6) 29 (4) 30 (4) Nasopharyngitis 11 (4) 30 (4) 29 (4) Urinary tract infection 7 (2) 14 (2) 11 (2) Bronchitis 6 (2) 9 (1) 6 (<1) Sinusitis 4 (1) 12 (2) 18 (3) Influenza 2 (<1) 8 (1) (1) Gastroenteritis 4 (1) 4 (<1) 5 (<1) Cystitis 3 (1) 1 (<1) 1 (<1) System Organ Class Preferred Term AJOVY 225 mg monthly N=290 n= (%) AJOVY 675 mg quarterly N=667 n= (%) Placebo N=668 n= (%) Herpes zoster 3 (1) 0 1 (<1) Injury, poisoning and procedural complications Ligament sprain 1 (<1) 3 (<1) 2 (<1) Investigations Blood creatine phosphokinase increased 1 (<1) 3 (<1) 7 (1) Alanine aminotransferase increased 1 (<1) 3 (<1) 1 (<1) Aspartate aminotransferase increased 1 (<1) 3 (<1) 1 (<1) Musculoskeletal and connective tissue disorders Back pain 3 (1) 11 (2) 9 (1) Musculoskeletal pain 3 (1) 4 (<1) 0 Arthralgia 3 (1) 2 (<1) 1 (<1) Nervous system disorders Dizziness 3 (1) 9 (1) 9 (1) Paraesthesia 2 (<1) 9 (1) 4 (<1) Migraine 1 (<1) 6 (<1) 11 (2) Respiratory, thoracic and mediastinal disorders Cough 1 (<1) 8 (1) 6 (<1) Skin and subcutaneous tissue disorders Pruritus 0 8 (1) 1 (<1) Injection site reactions The most frequently observed local reactions at the injection site were pain, induration and erythema.
Most local injection site reactions were transient and predominantly mild to moderate in severity. Pain, induration and erythema were typically observed immediately after injection while pruritus and rash appeared within a median of 24 and 48 hours, respectively.
Most injection site reactions resolved, generally within a few hours or days. If the intensity of Injection site reactions is severe, discontinuation of fremanezumab should be considered. 1 Clinical Trial Adverse Reactions – Pediatrics Over 400 pediatric patients with migraine, 6 to 17 years of age, have been treated with AJOVY in registration studies.
This included 123 pediatric patients in the placebo-controlled trial with episodic migraine (EM). The only adverse reactions of AJOVY observed in this study were injection site reactions, which is similar to the overall safety profile observed in adult clinical studies.
The injection site reactions reported were injection site erythema, injection site pain, and injection site swelling. Table 4 summarizes adverse reactions reported in the 3- month […]