Date: 2013-06-27
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of phase III results at the European Academy of Allergy and Clinical Immunology-World Allergy Organization (EAACI-WAO) World Allergy and Asthma Congress 2013 in Milan, Italy
Company: Novartis (Switzerland) Genentech, a member of Roche group (USA - Switzerland)
Product: omalizumab
Action
mechanism: Omalizumab is a biologic therapy unique in targeting immunoglobulin E (IgE). Research is ongoing to understand the mechanism of action of omalizumab in CIU/CSU, and to investigate its impact on the drivers of CIU/CSU. Omalizumab is approved for the treatment of severe allergic asthma under the brand-name Xolair® in more than 90 countries, including the US since 2003 and the EU since 2005. In the EU it is approved for the treatment of severe allergic asthma in children (aged six and above), adolescents, and adults. Following approval in the EU, a liquid formulation of Xolair in pre-filled syringes has been launched in most European countries.
Omalizumab is being jointly developed by Novartis and Genentech. In the US, Xolair® (omalizumab) for subcutaneous use in appropriate allergic asthma patients is co-promoted by Novartis Pharmaceuticals Corporation and Genentech.
Disease: moderate to severe refractory chronic idiopathic/spontaneous urticaria (CIU/CSU)
Therapeutic area: Dermatological diseases - Inflammatory diseases
Country:
Trial
details: GLACIAL is the second of three pivotal Phase III studies that investigate the efficacy and safety of omalizumab in chronic spontaneous urticaria. GLACIAL was a 40-week, global, multi-center, randomized double-blind study that evaluated the safety and efficacy of omalizumab compared to placebo. It 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.
ASTERIA II data have been published last February.
Latest
news: * On June 26, 2013, Novartis has announced today late-breaking results showing omalizumab met all primary and secondary endpoints of a pivotal Phase III safety registration study in chronic spontaneous urticaria (CSU). 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.
GLACIAL results supported the efficacy, safety and tolerability of omalizumab in patients with refractory CSU[Up to 40% of CSU patients fail on antihistamines, even those taking up to four times the approved dose. Antihistamines, at the approved dose, are currently the only licensed treatment for CSU.
Specifically, 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 (p<0.001). 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, p<0.001). 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, (p<0.001)), 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. This signified a marked improvement in patients\' quality of life.
Omalizumab-treated patients also experienced a significant increase in the proportion of days free of deep tissue swelling, also known as angioedema (p<0.001). 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.
Omalizumab is being jointly developed by Novartis and Genentech for CSU. Regulatory submissions for omalizumab in CSU are on track for later this year.
