6.1Clinical 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. Clinical Experience in Patients with gMG The safety of efgartigimod alfa in adult patients with gMG was established in a double blinded placebo- controlled study with efgartigimod alfa-fcab administered intravenously (Study 1) and its open-label extension, and in an active-controlled study of VYVGART HYTRULO administered subcutaneously (Study 3) and its open-label extension [see Clinical Studies (14.1) ].
Adverse Reactions with Efgartigimod Alfa-fcab Intravenous in Adult Patients with gMG In clinical studies, the safety of efgartigimod alfa-fcab administered intravenously in adult patients with gMG has been evaluated in 364 patients who received at least one dose of efgartigimod alfa-fcab. In Study 1, 84 patients received efgartigimod alfa-fcab 10 mg/kg [see Clinical Studies (14) ] . Of these 84 patients, approximately 75% were female, 82% were White, 11% were Asian, and 8% were of Hispanic or Latino ethnicity.
The mean age at study entry was 46 years (range 19 to 78). The minimum time to initiate a subsequent cycle, specified by study protocol, was 28 days from the last administration of the previous treatment cycle. On average, efgartigimod alfa-fcab-treated patients received 2 cycles in Study 1. The mean and median times to the second treatment cycle were 54 days and 50 days from the last administration of the first treatment cycle, respectively, for efgartigimod alfa-fcab-treated patients.
Adverse reactions reported in at least 5% of patients treated with efgartigimod alfa-fcab and more frequently than placebo are summarized in Table 1. The most common adverse reactions (reported in at least 10% of efgartigimod alfa-fcab-treated patients) were respiratory tract infection, headache, and urinary tract infection. Table 1: Adverse Reactions in at least 5% of Patients with gMG Treated with Efgartigimod Alfa-fcab Intravenously (EFG IV) and More Frequently than in Placebo-Treated Patients in Study 1 (Safety Population) Adverse reaction EFG IV (N=84) % Placebo (N=83) % Respiratory tract infection 33 29 Headache Headache includes migraine and procedural headache. 32 29 Urinary tract infection 10 5 Paraesthesia Paresthesia includes oral hypoesthesia, hypoesthesia, and hyperesthesia. 7 5 Myalgia 6 1 In a placebo-controlled study in patients with gMG who are anti-acetylcholine receptor (AChR) antibody negative (Study 2), 119 patients received one cycle of once-weekly administrations for 4 weeks of either efgartigimod alfa-fcab 10 mg/kg (n=58) or placebo (n=61).
The overall safety profile in Study 2 was consistent with the known safety profile of efgartigimod alfa-fcab in patients with gMG except for nausea, which occurred in 7% of anti-AChR antibody negative patients who received efgartigimod alfa-fcab compared to 5% of patients who received placebo. The safety of initiating subsequent cycles between 7 and 28 days from the last administration of the previous treatment cycle was assessed in another study in 60 patients (78% anti-AChR antibody positive and 22% anti-AChR antibody negative).
Of these patients, 63% were exposed to treatment for over a year when cycles were initiated less than 4 weeks after the last administration. Safety in these patients was similar to that seen in Study 1. Adverse Reactions with VYVGART HYTRULO in Patients with gMG In an active-controlled study in patients with gMG (Study 3), 110 patients were randomized and received one cycle of once weekly administrations for 4 weeks (4 administrations total), of either VYVGART HYTRULO subcutaneously (n=55) or efgartigimod alfa-fcab intravenously (n=55) at recommended doses [see Dosage and Administration (2.2) ] .
The open-label extension of Study 3 included 128 patients who switched from efgartigimod alfa-fcab IV to VYVGART HYTRULO. The most common adverse reactions (reported in at least 10% of VYVGART HYTRULO-treated patients) were injection site reactions and headache. In Study 3, injection site reactions occurred in 38% of patients receiving VYVGART HYTRULO. These were injection site rash, erythema, pruritus, bruising, pain, and urticaria.
In Study 3 and its open-label extension (n = 168), all injection site reactions were mild to moderate in severity and did not lead to treatment discontinuation. The majority occurred within 24 hours after administration and resolved spontaneously. Most injection site reactions occurred during the first treatment cycle, and the incidence decreased with each subsequent cycle. Clinical Experience in Patients with CIDP Adverse Reactions with VYVGART HYTRULO in Patients with CIDP In a placebo-controlled study in patients with CIDP (Study 4, stage B), 221 patients were randomized to receive once-weekly administration of either VYVGART HYTRULO 1,008 mg /11, 200 units subcutaneously (n=111) or placebo (n=110) [see Clinical Studies (14.2) ].
The mean duration of treatment with VYVGART HYTRULO in stage B was 25 weeks. The overall safety profile observed in patients with CIDP treated with VYVGART HYTRULO was consistent with the known safety profile of VYVGART HYTRULO and of efgartigimod alfa-fcab administered intravenously. In Study 4, injection site reactions occurred in 15% of patients treated with VYVGART HYTRULO compared to 6% of patients who received placebo.
The most common of these injection site reactions were injection site bruising and injection site erythema. All injection site reactions were mild to moderate in severity. Most injection site reactions occurred during the first 3 months of treatment.
