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Novartis has announced the results of GLACIAL, a Phase III safety registration study in treatment of chronic spontaneous urticaria (CSU) with omalizumab. Omalizumab is a targeted therapy unique in binding to immunoglobulin E (IgE). It is not currently approved or indicated for CSU. Omalizumab met all primary and secondary endpoints of the study in CSU, a chronic and debilitating form of hives with limited approved treatment options. The data was presented for the first time at the European Academy of Allergy and Clinical Immunology-World Allergy Organization (EAACI-WAO) World Allergy and Asthma Congress 2013 in Milan, Italy. Omalizumab is not currently approved or indicated for CSU. Regulatory submissions for omalizumab in CSU are on track for later this year.

GLACIAL is the second of three pivotal Phase III studies that investigate the efficacy and safety of omalizumab in CSU. The study results supported the efficacy, safety and tolerability of omalizumab in patients with refractory CSU. GLACIAL was a 40-week, global, multi-center, randomized double-blind study that involved 335 patients aged between 12 and 75 with moderate- to-severe refractory CSU despite receiving standard-of-care therapy, consisting of concomitant H1 antihistamine therapy (up to four times the approved dose) and other background medications including H2 antihistamines and/or leukotriene receptor antagonists (LTRAs). Patients were randomized to omalizumab 300 mg or placebo (3:1), given subcutaneously every four weeks for a total period of 24 weeks.

More than one third of omalizumab-treated patients in the GLACIAL study were completely itch- and hive-free by Week 12, compared to 5% of placebo-treated patients. During the same time period, the proportion of patients with well controlled CSU symptoms (itch, hives) was four times higher in the omalizumab group compared to placebo (52% and 12% respectively). The significant improvements observed with omalizumab were sustained throughout the treatment period up to Week 24.

The study also evaluated impact on quality of life, an important measure as up to 80% of patients with CSU suffer negative effects on their quality of life including sleep deprivation and psychological comorbidities such as depression and anxiety. Patients receiving omalizumab experienced nearly double the improvement in a quality of life measure compared to placebo (reduction of 9.7 and 5.1 respectively), as assessed by improvement from baseline in the Dermatology Life Quality Index (DLQI). This is significant, given that at the start of the study patients in both groups had a baseline score of over 12, indicating a severe impact on a patient's quality of life. Omalizumab reduced the score by nearly 10 points by Week 12, lowering the DLQI score to 2.3.

Omalizumab-treated patients also experienced a significant increase in the proportion of days free of deep tissue swelling, also known as angioedema. Angioedema is a painful and disfiguring condition experienced by approximately 40%-50% of patients with CSU.

In the study, the incidence and severity of adverse events (AEs) was similar between omalizumab and placebo recipients, with no new safety issues identified. There were no major imbalances in AEs, with the exception of headache and upper respiratory tract infections, which were more common in the omalizumab group; and sinus congestion, migraine and idiopathic urticaria, which were more common in the placebo group.

The key efficacy endpoint was assessed by the weekly Itch Severity Score (ISS), on a 21-point scale. The study showed that omalizumab significantly improved the mean weekly ISS from baseline by 8.6 (p<0.001), compared to a 4.0 improvement in patients on placebo. Disease control was also assessed by a measure of itch and hives called the weekly urticaria activity score (UAS7), where any score of 6 or less out of a 42 point score is considered to represent a well-controlled disease and a score of zero represents a complete resolution of symptoms.

Seven (2.8%) patients experienced SAEs in the omalizumab group, compared to three (3.6%) in the placebo group. No deaths were reported during this study.

It is the first study to evaluate omalizumab as concomitant therapy beyond H1 antihistamines, also including H2 antihistamines and/or LTRAs in refractory CSU patients. The study results supported the safety and effectiveness of omalizumab in patients with refractory CSU.

CSU is also known as chronic idiopathic urticaria (CIU) in the US, and is a severe and distressing skin condition characterized by red, swollen, itchy and sometimes painful hives or wheals on the skin that spontaneously present and re-occur for more than six weeks. There is no approved treatment for CSU that is broadly effective in more than 50% patients who are not responding to approved doses of antihistamines, the mainstay of current symptomatic therapy.