Omalizumab met all primary and secondary endpoints in pivotal GLACIAL study of patients with refractory chronic spontaneous urticaria (CSU)
Omalizumab found to be effective, safe and well tolerated in refractory CSU patients, including those on antihistamines at up to four times the approved dose
By Week 12 omalizumab eliminated or suppressed symptoms in more than half of patients who failed multiple therapies; benefit sustained during active treatment
Basel, June 26, 2013 - Novartis 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), a chronic and debilitating form of hives with limited approved treatment options[2-4]. 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, a chronic and debilitating skin disease with intractable itch and hives. 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.
"This is encouraging news for people living with CSU, whose quality of life is greatly impacted by this serious disease and who currently have few treatment options," said Tim Wright, Global Head of Development, Novartis Pharmaceuticals. "Novartis is committed to doing all we can for these patients by working to develop an important advance in CSU treatment, where unmet medical need remains high."
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.
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. Medical guidelines allow for increased doses of antihistamines, up to four times the approved dose, to increase symptom control in some patients. At any given time, the prevalence of CSU is 0.5% to 1% worldwide.
Omalizumab is being jointly developed by Novartis and Genentech, Inc. for CSU. Regulatory submissions for omalizumab in CSU are on track for later this year.
About the GLACIAL Study
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.
Omalizumab met all pre-specified primary and secondary endpoints in the study. The safety endpoints assessed AEs, serious AEs (SAEs), antibody data and changes in vital signs/laboratory evaluations. Efficacy endpoints included weekly itch severity, health-related quality of life, number of angioedema-free days, weekly hive scores (number, size), reduction or elimination of disease symptoms (itch, hives) and the time it took to achieve a clinically significant benefit.
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.
About Omalizumab (Xolair®)
Omalizumab is a targeted therapy unique in binding to immunoglobulin E (IgE). It is not currently approved or indicated for CSU. Research is ongoing to understand the mechanism of action of omalizumab in CSU, and to investigate its impact on the drivers of CSU. It may suppress histamine-induced skin reactions through its reduction of IgE and downstream effects on cellular activation mechanisms.
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. In the US, Xolair (omalizumab) for subcutaneous use in appropriate allergic asthma patients is co-promoted by Novartis Pharmaceuticals Corporation and Genentech, Inc.
As an investigational compound, the safety and efficacy profile of omalizumab has not been established in CSU. Omalizumab has been available for CSU through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. For various reasons, including the uncertainty of clinical trials, there is no guarantee that omalizumab will become commercially available for CSU anywhere in the world.
About Novartis in Specialty Dermatology
Novartis is committed to developing innovative, life-changing specialty dermatology therapies to redefine treatment paradigms and transform patient care in severe skin diseases where there are remaining high unmet medical needs. The Novartis specialty dermatology portfolio includes two unique targeted products in Phase III development, omalizumab (Xolair®) for CSU and AIN457 (secukinumab) for moderate-to-severe plaque psoriasis. There are also more than 10 compounds in early stage development for a wide range of severe skin diseases in the Novartis specialty dermatology portfolio.
The foregoing release contains forward-looking statements that can be identified by terminology such as "on track," "encouraging," "committed," "working to develop," "ongoing," "investigational," "potential," "will," or similar expressions, or by express or implied discussions regarding potential new indications or labeling for omalizumab, potential marketing approvals for AIN457 or any other dermatology products, or regarding potential future revenues from omalizumab, AIN457 or such other products. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that omalizumab will be approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that AIN457 or any other dermatology products will be submitted or approved for sale in any market, or at any particular time. Neither can there be any guarantee that omalizumab, AIN457 or any such other products will achieve any particular levels of revenue in the future. In particular, management's expectations regarding omalizumab could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
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 Maurer M, Staubach P, Ashby M, et al. The safety and efficacy of omalizumab in chronic idiopathic/spontaneous urticaria (CIU/CSU): results from a Phase III randomized, double-blind, placebo-controlled study. European Academy of Allergy and Clinical Immunology-World Allergy Organization (EAACI-WAO) World Allergy and Asthma Congress annual meeting 2013. Late Breaking Poster. 25 June 2013, 12:00 p.m.
 Asthma and Allergy Foundation of America (AAFA) website. "Chronic Urticaria (Hives)." http://www.aafa.org/display.cfm?id=9&sub=23&cont=328. Accessed November 14, 2012.
 American Academy of Allergy Asthma & Immunology (AAAAI) website. "Skin Allergy Overview." http://www.aaaai.org/conditions-and-treatments/allergies/skin-allergy.aspx. Accessed November 14, 2012.
 Casale T, Maurer M, Hsieh HJ, et al. Efficacy and safety of omalizumab in chronic idiopathic/spontaneous urticaria: results from a phase III, randomized, double-blind, placebo-controlled trial (ASTERIA II). American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting. 4611 Late Breaking Oral Abstract I. 25 March 2013, 2:30 pm.
 Sánchez-Borges M, Asero R, Ansotegui IJ, et al. Diagnosis and treatment of urticaria and angioedema: a worldwide perspective (position paper). World Allergy Organization Journal. 2012; 5:125-147.
 Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy 2011; 66: 317-330.
 Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY, et. al. Translating the science of quality of life into practice: What do dermatology life quality index scores mean?. J Invest Dermatol. 2005 Oct;125(4):659-64.
 European Medicines Evaluation Agency. Omalizumab (XOLAIR). Summary of product characteristics. Available at: www.ema.europa.eu. Accessed 7 June, 2013.
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