Novartis advances ligelizumab (QGE031) in urticaria to Phase III on basis of strong Phase II head-to-head data

• PEARL 1 and PEARL 2, the largest pivotal trials to date in chronic spontaneous urticaria (CSU), will enroll more than 2,000 CSU patients[1],[2]
   
• Ligelizumab (QGE031), a monoclonal antibody, is being developed as a treatment option for CSU patients whose symptoms are inadequately controlled by H1-antihistamines[3]
   
• In a head-to-head study, ligelizumab showed improvements over Xolair® (omalizumab) in CSU patients[4]

Basel, December 4, 2018 - Novartis, a leader in immuno-dermatology, announced today the initiation of Phase III trials for ligelizumab (QGE031) - a high-affinity monoclonal anti-IgE antibody - in chronic spontaneous urticaria (CSU) patients whose symptoms are inadequately controlled by H1-antihistamines[1],[2]. Phase III studies PEARL1 and PEARL 2 are planned to include more than 2,000 CSU patients[1],[2].

"CSU has a big impact on patients' lives," said Marcus Maurer, MD, Professor of Dermatology and Allergy and Director of Research at the Department of Dermatology and Allergy, Allergie-Centrum-Charité of the Charité-Universitätsmedizin in Berlin, Germany. "Despite existing treatment options, too many people continue to struggle with the debilitating and potentially painful symptoms of CSU. Advancing ligelizumab to Phase III is encouraging news for physicians and patients who have difficulty in controlling symptoms."

Results from the placebo- and active-controlled Phase IIb trial showed that ligelizumab met the primary endpoint by demonstrating a clear dose-response relationship, and improvements over Xolair^® (omalizumab) in CSU patients[4]. Ligelizumab achieved rapid onset of action and improved and sustained efficacy in CSU patients, whose symptoms are not adequately controlled by H1-antihistamines[4].

"Novartis is committed to leveraging our strong heritage and expertise in immuno-dermatology to reimagine and discover potential new treatments which can benefit patients," said Eric Hughes, Global Development Unit Head, Immunology, Hepatology and Dermatology. "By initiating ligelizumab to Phase III studies we continue to honor that commitment."

The purpose of Phase III studies PEARL 1 and PEARL 2 is to establish efficacy and safety of ligelizumab in adolescent and adult patients >= 12 years of age with CSU who remain symptomatic despite the use of H1-antihistamines[1],[2]. Both trials are multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group studies[1],[2] in 48 countries including the US, Germany and Japan[5].

About Novartis in CSU
Advancing ligelizumab further strengthens the immuno-dermatology pipeline of Novartis. Novartis currently also markets Xolair. Xolair, indicated as an add-on therapy for the treatment of CSU[6], is the only therapy recommended by the global guideline on chronic urticaria (CU) for patients unresponsive to antihistamines[7]. In the US, Novartis Pharmaceuticals Corporation and Genentech work together to develop and co-promote Xolair.

About CSU
CSU is a severe, unpredictable skin condition that, if not or only partially controlled, has a major impact on the quality of sleep and the social and working lives of patients[8],[9]. Symptoms include spontaneous swelling of the skin and the appearance of itchy hives which can have a profoundly negative impact on patients' sleep, work productivity and subsequent health-related quality of life[8],[9]. Recent data publications suggested that some patients with CSU still report high disease burden despite previous treatment with urticaria medication such as H₁-/H₂-antihistamines or montelukast, with two thirds still having severe activity (UAS7 >=28) and more than half reporting a very large effect of CSU on their life (DLQI >10). Employed CSU patients also report a high negative impact on their work[8]-[12].

About PEARL 1 and PEARL 2
PEARL 1 and 2 are Phase III, multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group studies designed to establish efficacy and safety of ligelizumab in adolescent and adult subjects with CSU who remain symptomatic despite H1-antihistamine treatment by demonstrating better efficacy over Xolair (omalizumab)[1],[2]. More than 2,000 patients will initially be randomized to ligelizumab dose A, ligelizumab dose B, omalizumab 300mg with treatment given every 4 weeks for one year[1],[2]. Patients initially randomized to placebo will be switched to ligelizumab dose B starting week 24 until week 52[1],[2]. The primary outcome will measure absolute change from baseline in UAS7 at Week 12[1],[2].

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. 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 is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach nearly 1 billion people globally and we are finding innovative ways to expand access to our latest treatments. About 125 000 people of more than 140 nationalities work at Novartis around the world. Find out more at www.novartis.com.

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References
      [1]   ClinicalTrials.gov. A Phase III Study of Efficacy and Safety of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines. Available online at: https://clinicaltrials.gov/ct2/show/NCT03580369. Last accessed September 2018.
      [2]   ClinicalTrials.gov. A Phase III Study of Efficacy and Safety of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines. Available online at: https://clinicaltrials.gov/ct2/show/NCT03580356. Last accessed September 2018.
      [3]   Maurer M, et al. Ligelizumab as add-on therapy for patients with H1-antihistamine-refractory chronic spontaneous urticaria: Primary results of a placebo- and active-controlled phase 2b dose finding study. EAACI 2018 QGE031 C2201 Primary Results.
      [4]   Maurer M et al. Ligelizumab achieves rapid onset of action, improved and sustained efficacy compared with omalizumab in patients with chronic spontaneous urticaria not adequately controlled by H1 antihistamines. Oral presentation OP 01.03 at 27^th EADV Congress 2018. 13^th September 2018.
      [5]   Data on file
      [6]   EU Xolair Summary of Product Characteristics. Novartis Europharm Limited. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000606/human_med_001162.jsp&mid=WC0b01ac058001d124. Last accessed September 2018.
      [7]   Zuberbier T et al. The EAACI/GA²LEN/EDF/WAO Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. Allergy 2018; 73:1393-1414
      [8]   Sánchez-Borges M, et al. Diagnosis and Treatment of Urticaria and Angioedema: A Worldwide Perspective. WAO Journal 2012; 5: 125-147.
      [9]   O'Donnell BF, et al. The impact of chronic urticaria on the quality of life. British Journal of Dermatology 1997; 136: 197-201.
      [10] Maurer M, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy 2011; 66: 317-330.
      [11] Kang MJ, et al. The Impact of Chronic Idiopathic Urticaria on Quality of Life in Korean Patients. Annals of Dermatology 2009; 21: 226-229.
      [12] Maurer M et al. The burden of chronic spontaneous urticaria in substantial: Real-world evidence from ASSURE-CSU. Allergy 2017. Advanced online publication. DOI:19.111/all.13209.

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