Novartis announces positive results from final Phase III omalizumab registration study in severe form of chronic skin disease CSU

Omalizumab significantly reduced itch and hives caused by chronic spontaneous urticaria (CSU) as early as Week 1; benefit sustained over 24 weeks of active treatment[1]

Omalizumab 300 mg was nearly twice as effective in improving patients’ quality of life within 12 weeks of treatment versus placebo[1]

ASTERIA I is the final omalizumab CSU registration study to be presented; regulatory applications were filed with EU and US authorities in Q3 2013

CSU is a debilitating form of hives and chronic itch; more than 50% of patients do not respond to approved doses of antihistamines, the only licensed treatment

Basel, October 5, 2013 – Novartis announced today new results from the Phase III ASTERIA I study showing omalizumab was effective and safe in the treatment of chronic spontaneous urticaria (CSU)[1], 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 today for the first time at the 22nd Congress of the European Association of Dermatology and Venereology (EADV) in Istanbul, Turkey. Omalizumab is currently not approved for the treatment of CSU.

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[2],[3]. 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.

“The positive new data clearly show the potential of omalizumab to treat CSU, a disease where more than 50% of patients don’t respond to approved doses of antihistamines, the only licensed treatment option,” said Tim Wright, Global Head of Development, Novartis Pharmaceuticals. “With submissions to EU and US regulatory authorities now completed, we are on track to bring omalizumab to people suffering from this chronic and debilitating disease.”

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)[1]. 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[1]. This benefit was maintained throughout active treatment (Week 24)[1].

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)[1]. 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[4].

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)[1]. 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)[1].

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[1]. No deaths were reported during this study[1].

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[5],[6] that spontaneously present and re-occur for more than six weeks[2]. At any given time, the prevalence of CSU is 0.5% to 1% worldwide[4].

Omalizumab is being jointly developed by Novartis and Genentech, Inc. for CSU.

About the ASTERIA I Study
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[1].

The primary endpoint, ISS at Week 12, was assessed via a 21-point scale at Week 12[1]. 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[1].

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)[1]. 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[1]. In addition, time to response was measured by the median time to Minimally Important Difference (MID)[1].

About Omalizumab (Xolair®)
Omalizumab is a targeted therapy unique in binding to immunoglobulin E (IgE). It is currently not approved for the treatment of CSU. Omalizumab suppresses histamine-induced skin reactions, probably through its reduction of IgE and downstream effects on cellular activation mechanisms[7]. Research is ongoing to understand the mechanism of action of omalizumab in CSU, which could lead to deeper understanding of how the disease develops[8].

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. 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.

About Novartis in specialty dermatology
Novartis is committed to developing innovative, life-changing specialty dermatology therapies redefining treatment paradigms and transforming 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 secukinumab (AIN457) 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.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as “potential,” “on track” “can,” “ongoing,” “could,” “committed,” 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 such 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 these products 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; competition in general; government, industry and general public pricing pressures; unexpected manufacturing issues; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; 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 131,000 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] Maurer M. Phase III randomized, double-blind, placebo-controlled study evaluating efficacy and safety of omalizumab in H1-antihistamine-refractory chronic idiopathic/spontaneous urticarial. European Academy of Dermatology and Venereology (EADV) annual meeting 2013. Oral Presentation. 5 October 2013, 11:30 a.m.
[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] Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013 Jul;132(1):101-9. doi: 10.1016/j.jaci.2013.05.013.
[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] European Medicines Evaluation Agency. Omalizumab (XOLAIR). Summary of product characteristics. Available at: www.ema.europa.eu. Accessed 7 June, 2013.
[8] 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.

SOURCE: Novartis