Novartis reports Phase III data showing omalizumab improved itch in patients with a chronic form of hives who failed standard therapy[1]

• Study published in NEJM today and presented tomorrow met primary endpoint[1] in moderate to severe refractory chronic idiopathic/spontaneous urticaria (CIU/CSU)
   
• Up to two-thirds (66%) of omalizumab patients had their itch and hives well controlled within 12 weeks of initiating treatment, versus 19% for placebo[2],[3]
   
• CIU/CSU can be a serious, debilitating form of hives; critical unmet need among >50% of patients who don't achieve relief with approved antihistamine doses[4]
   
• Omalizumab is a biologic therapy that targets the IgE antibody; further Phase III studies in CIU/CSU and regulatory submissions on track for 2013

Basel, February 24, 2013 - Late-breaking 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 antihistamine doses[1].

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% and 19% respectively)[2],[3]. The data were published today 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[5],[6] spontaneously presenting and reoccurring for more than six weeks[3]. Angioedema, or deep tissue swelling, also occurs in approximately 40 to 50% of these patients[7]. While antihistamines are commonly used to treat CIU/CSU, there is still a critical unmet need among patients, with more than 50% not achieving relief with approved doses[2].

"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[1]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[2]. The omalizumab 75 mg dose group did not demonstrate statistical significance compared to placebo[1].

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[1]. Sixty-six percent of patients in the omalizumab 300 group and 43% in the 150 mg group experienced well controlled disease by Week 12, compared to 19% in the placebo group[2]. 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[2],[3].

The incidence and severity of adverse events (AEs) was similar across treatment groups[1]. 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[2].

CIU/CSU also has negative effects on quality of life, which frequently includes sleep deprivation and psychiatric comorbidity[4]. At any given time, the prevalence of CIU/CSU is 0.5% to 1% worldwide[4].There is no approved treatment for CIU/CSU that is broadly effective in patients who are refractory to antihistamines, the mainstay of current symptomatic therapy[4].

Study Details
ASTERIA II was a global, multi-center, 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[1]. 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 period². 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[2].

Five (6.3%) patients experienced serious AEs (SAEs) in the omalizumab 300 mg dose group, compared to two (2.5%) in the placebo group[2]. In the 150 mg and 75 mg dose groups, one patient experienced SAEs in each group (1.1% and 1.3%, respectively). No deaths were reported during this study[2].

About Omalizumab
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[7]. 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.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "on track," "will," "could," "potentially," "committed," "look forward to," or similar expressions, or by express or implied discussions regarding potential new indications or labeling for omalizumab or regarding potential future revenues from omalizumab. 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 with omalizumab 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. Nor can there be any guarantee that omalizumab 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; 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.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 128,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.

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References
[1] Casale T, Maurer M, Hsieh HJ, et al. Efficacy and safety of omalizumab in chronic idiopathic/spontaneous urticarial (CIU/CSU): results from a phase III, randomized, double-blind, placebo-controlled trial. JACI Vol. 131, No. 2 February, 2013 p 1A-4A-Supplement.
[2] Maurer M, Rosén K, Hsieh HJ, et al Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. NEJM 2013; DOI: 10.1056/NEJMoa1215372.
[3] Casale T, Maurer M, Hsieh HJ, et al. Efficacy and safety of omalizumab in chronic idiopathic/spontaneous urticarial: 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.
[4] 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.
[5] 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.
[6] 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.
[7] 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.
[8] Saini S, Rosen KE, Hsieh HJ, et al. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol 2011;128(3):567-573.

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