Safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU): Pooled analysis of three randomized, double-blind, placebo-controlled phase III studies (ASTERIA I, ASTERIA II, and GLACIAL)

Background: The safety profile of omalizumab, a humanized anti-IgE monoclonal antibody, for the treatment of moderate-to-severe allergic asthma is well-established. Omalizumab is the first and only approved (Europe and US) therapy for the treatment of chronic spontaneous/idiopathic urticaria (CSU/CIU) in adult and adolescent (≥12 years) patients with inadequate response to H₁-antihistamines. Here we report the pooled safety data from 975 patients in three Phase III studies (ASTERIA I, ASTERIA II and GLACIAL).

Methods: Patients in ASTERIA I and ASTERIA II were symptomatic despite approved doses of H₁-antihistamines and were randomized to receive omalizumab 75 mg, 150 mg or 300 mg, or placebo. Patients in GLACIAL received omalizumab 300 mg or placebo and were symptomatic despite H₁-antihistamines (up to 4X approved dose) plus H₂-antihistamines, leukotriene-receptor antagonists or both. Safety was evaluated at Week 12 (treatment period for ASTERIA II and a pre-specified timepoint in ASTERIA I and GLACIAL), and Week 24 (treatment period for ASTERIA I and GLACIAL).

Results: The overall incidence of adverse events (AEs:≥1) was similar across studies between patients receiving omalizumab 75 mg (68.5%), 150 mg (74.9%), 300 mg (77.7%) vs placebo (68.6%). The majority of treatment-related AEs were mild or moderate in severity across treatment groups. Incidence of AEs of special interest such as injection site reactions and arterial thrombotic events were low and similar across studies for omalizumab vs placebo. Frequency of AEs reported to be caused by omalizumab was similar with placebo for 12- or 24-week treatment periods. No additional AEs of special interest were identified in the studies. The overall incidence of serious AEs (SAEs) was similar between patients receiving omalizumab 75 mg (2.1%), 150 mg (3.4%), 300 mg (6.1%) vs placebo (5.0%). No SAEs were suspected to be caused by omalizumab or led to withdrawal from treatment. No anaphylactic reactions, malignancies or deaths related to omalizumab were observed during the studies. No patient developed anti-omalizumab antibodies.

Conclusions: No new safety signals were identified compared with the established safety profile of omalizumab for the treatment of moderate-to-severe allergic asthma. Safety data was similar for all omalizumab-treated groups and placebo for both Week 12 and 24 treatment periods. Safety data to-date support omalizumab as a well-tolerated treatment option for patients with CSU/CIU.