Date: 2013-10-05
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 22nd Congress of the European Association of Dermatology and Venereology (EADV) in Istanbul, Turkey
Company: Novartis (Switzerland)
Product: omalizumab
Action
mechanism: Omalizumab is a monoclonal antibody binding to immunoglobulin E (IgE). It suppresses histamine-induced skin reactions, probably through its reduction of IgE and downstream effects on cellular activation mechanisms. Research is ongoing to understand the mechanism of action of omalizumab in CSU, which could lead to deeper understanding of how the disease develops.
Omalizumab is approved for the treatment of moderate to severe persistent 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 persistent allergic asthma in children (aged six and above), adolescents, and adults. Omalizumab is being jointly developed by Novartis and Genentech, Inc. for CSU.
Disease: chronic spontaneous urticaria (CSU)
Therapeutic area: Dermatological diseases
Country:
Trial
details: ASTERIA I was a 40-week, global, multi-center, randomized double-blind study that evaluated the efficacy and safety of omalizumab compared to placebo. It involved 318 patients between the ages of 12 and 75 with moderate-to-severe CSU who remained symptomatic despite prior treatment with H1 antihistamine treatment. Patients were randomized to omalizumab 300 mg, 150 mg, 75 mg or placebo (1:1:1:1), given subcutaneously every four weeks for a total period of 24 weeks, and subsequently monitored during a 16 week follow-up period when there was no active treatment. The primary endpoint, ISS at Week 12, was assessed via a 21-point scale at Week 12. Omalizumab significantly improved the mean weekly ISS from baseline by 9.4 in the 300 mg treatment arm (p<0.0001), 6.7 in the 150 mg treatment arm (p=0.0012) and 6.5 in the 75 mg treatment arm (p=0.0010), compared to a 3.6 improvement in patients on placebo.
Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) questionnaire (range of 0-30, with a higher score representing greater impairment). Control of CSU symptoms was 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. In addition, time to response was measured by the median time to Minimally Important Difference (MID).
Latest
news: * On October 5, 2013, Novartis has announced new results from the Phase III ASTERIA I study showing omalizumab was effective and safe in the treatment of chronic spontaneous urticaria (CSU, a chronic and debilitating form of hives. ASTERIA I is the final pivotal registration study for omalizumab in CSU to be announced, and results were presented at the 22nd Congress of the European Association of Dermatology and Venereology (EADV) in Istanbul.
The ASTERIA I data support the positive and consistent results from two previously reported pivotal Phase III registration studies of omalizumab in CSU (ASTERIA II and GLACIAL), which were presented at major medical congresses earlier this year. Regulatory applications for omalizumab in CSU were filed with US and EU health authorities in the third quarter of 2013, based on data from nearly 1,000 patients included in these Phase III studies.
Specifically, the ASTERIA I study showed that patients treated with omalizumab responded as early as Week 1 (300 mg dose), compared to Week 4 in the placebo group (p=<0.0001). By Week 12 all three omalizumab doses (300 mg, 150 mg and 75 mg) were significantly superior to placebo in improving patients\' weekly Itch Severity Score (ISS), which was the primary endpoint of the study. This benefit was maintained throughout active treatment (Week 24). The study also showed patients treated with omalizumab 300 mg experienced nearly twice the improvement in their quality of life compared to those taking placebo by Week 12 (p<0.0001). Quality of life measures are critical to assessing CSU treatments, because the disease can frequently lead to other negative consequences such as sleep deprivation, depression and anxiety. In addition, by Week 12 more than half (52%) of omalizumab 300 mg patients in the study had their CSU symptoms (itch, hives) well controlled and 36% had no symptoms at all (p<0.0001). At the same time point, omalizumab 300 mg treated patients also experienced a significant increase in the proportion of days free of deep tissue swelling, also known as angioedema (p<0.0001).
The study met all pre-specified secondary efficacy endpoints for omalizumab 300 mg and 150 mg compared to placebo, except the 150 mg group did not reach statistical significance versus placebo for the quality of life measurement at Week 12.
The incidence and severity of adverse events (AEs) was similar across all ASTERIA I treatment groups. Five omalizumab patients experienced serious AEs during the treatment period (75 mg group n=2, 150 mg group n=3, 300 mg group n=0), compared to four patients in the placebo group. No deaths were reported during this study.
