Novartis has announced results from ASTERIA II, a phase III placebo-controlled study, demonstrated that omalizumab provided effective treatment in patients with moderate to severe refractory chronic idiopathic urticaria (CIU), also referred to as chronic spontaneous urticaria (CSU), who remain symptomatic despite treatment with approved anti-histamine doses.

At the end of the treatment period (week 12), more than three times as many omalizumab 300 mg patients had well controlled disease compared to placebo (66 per cent and 19 per cent respectively). The data were published in the New England Journal of Medicine and will be presented tomorrow at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in San Antonio, Texas, USA. Omalizumab is not indicated for CIU/ CSU.

CIU/CSU is a distressing skin condition characterized by red, swollen, itchy and sometimes painful hives on the skin spontaneously presenting and reoccurring for more than six weeks. Angioedema, or deep tissue swelling, also occurs in approximately 40 to 50 per cent of these patients. While anti-histamines are commonly used to treat CIU/CSU, there is still a critical unmet need among patients, with more than 50 per cent not achieving relief with approved doses.

"These results indicate that omalizumab could potentially be an important addition in the treatment of chronic idiopathic or spontaneous urticaria, a disease that can have a significant impact on patients and can be challenging to manage," said Tim Wright, Global Head of Development, Novartis Pharmaceuticals. "We are committed to helping patients with this disease and look forward to receiving further results from ongoing longer-term clinical trials."

ASTERIA II is the first phase III data to be presented from a clinical trial program in CIU/CSU, which also includes two additional studies investigating the efficacy and safety of omalizumab over 12 and 24 weeks treatment duration. Novartis regulatory submissions are on track for 2013.

The ASTERIA II study evaluated the efficacy and safety of omalizumab in patients aged 12 to 75 years of age with moderate to severe refractory CIU/CSU despite receiving concomitant antihistamine therapy at approved doses, within a 12 week treatment period. The primary endpoint was measured using a 21 point scale known as a weekly Itch Severity Score (ISS). The study met its primary endpoint, showing that omalizumab given at doses of 150 and 300 mg every four weeks for 12 weeks, significantly improved the mean weekly ISS from baseline (approximately 14 in all treatment groups) by 8.1 (p=0.001) and 9.8 (p<0.001), respectively, compared to a 5.1 improvement in patients on placebo. The omalizumab 75 mg dose group did not demonstrate statistical significance compared to placebo.

Patient response, as measured by the median time to Minimally Important Difference (MID), a secondary endpoint, occurred as early as Week 1 (300 mg dose) and Week 2 (150 mg dose), compared to Week 4 in the placebo group. Sixty-six per cent of patients in the omalizumab 300 group and 43 per cent in the 150 mg group experienced well controlled disease by Week 12, compared to 19 per cent in the placebo group. In the study, disease control was assessed by a weekly urticaria activity score (UAS7), where any score of 6 or less out of a 42 point score is considered to represent well controlled disease.

The incidence and severity of adverse events (AEs) was similar across treatment groups. There were no major imbalances in any of the system organ class AEs, with the exception of headache, where more cases were reported in the 150 mg omalizumab group compared with placebo.

CIU/ CSU also has negative effects on quality of life, which frequently includes sleep deprivation and psychiatric comorbidity. At any given time, the prevalence of CIU/CSU is 0.5 per cent to one per cent worldwide. There is no approved treatment for CIU/ CSU that is broadly effective in patients who are refractory to anti-histamines, the mainstay of current symptomatic therapy.

ASTERIA II was a global, multi-centre, randomized double-blind study that evaluated the efficacy and safety of omalizumab compared to placebo and involved 323 patients aged between 12 and 75 with moderate to severe CIU/ CSU. Patients were randomized to omalizumab 75 mg, 150 mg or 300 mg or placebo, given subcutaneously every four weeks, for a total of three doses within a 12-week treatment period, with a 16-week follow-up period. Omalizumab 150 mg and 300 mg dose groups met the pre-specified primary endpoint and all pre-specified secondary endpoints in the ASTERIA II trial, except for the 150 mg dose that did not show a significant difference from placebo in the proportion of angioedema-free days from Week 4 to Week 12 of therapy.

Five (6.3 per cent) patients experienced serious AEs (SAEs) in the omalizumab 300 mg dose group, compared to two (2.5 per cent) in the placebo group. In the 150 mg and 75 mg dose groups, one patient experienced SAEs in each group (1.1 per cent and 1.3 per cent, respectively). No deaths were reported during this study.

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.