? is the first treatment to receive FDA Breakthrough Therapy designation in chronic spontaneous urticaria (CSU) in patients with an inadequate response to H1-antihistamines1
?Currently there are limited approved therapies for patients with CSU, also known as chronic idiopathic urticaria (CIU)
?Breakthrough Therapy designation suggests ligelizumab has the potential to provide a substantial benefit over existing available treatments
?U.S. regulatory filing in CSU is anticipated in 2022

Basel, January 14, 2021 — Novartis today announced that the U.S. Food and Drug Administration (FDA) has granted ligelizumab (QGE031) Breakthrough Therapy designation for the treatment of chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria (CIU), in patients who have an inadequate response to H1-antihistamine treatment.

CSU is an unpredictable and severe disease of the skin, affecting 0.5-1% of the global population at any time2. It is characterized by the development of itchy, painful wheals (hives), swelling (angioedema), or both, lasting for at least 6 weeks and occurring with no known cause3. CSU can be challenging or frustrating for patients due to the severity and unpredictable nature4. It most commonly persists for 1-5 years, but in some cases even longer2.

“Chronic spontaneous urticaria is a debilitating disease that may significantly impact a patient’s life. With so few treatment options available, patients are looking for more and better therapies to control their disease,” said Angelika Jahreis MD, PhD, Novartis Global Head Development Unit Immunology, Hepatology & Dermatology. “The FDA Breakthrough Therapy designation recognizes the need for a more effective treatment for this unpredictable, systemic and debilitating disease.”

According to FDA guidelines, treatments that receive Breakthrough Therapy Designation must target a serious or life-threatening disease and demonstrate a potential substantial improvement over existing therapies on one or more significant clinical endpoints5.

About ligelizumab
Ligelizumab (QGE031) is a next generation monoclonal anti-immunoglobulin E (IgE) antibody. Ligelizumab is thought to work by blocking the IgE/Fc?RI pathway, a key driver of the inflammatory process in CSU6,7. In a Phase IIb dose-finding trial, more patients experienced complete resolution of wheals (hives) with ligelizumab compared with Xolair® (omalizumab)8. No safety concerns were found with ligelizumab compared with omalizumab or placebo in a Phase IIb dose-finding trial in CSU patients with inadequate control on antihistamines8. Ligelizumab compared with omalizumab is currently being investigated in ongoing Phase III clinical trial programs including PEARL 1 and PEARL 2 (NCT03580369 and NCT03580356). The clinical trials have recruited more than 2,000 patients globally across 48 countries and results are expected in the second half of 20219,10.

About Novartis in CSU
Novartis is curious about the science beneath the skin and dedicated to reimagining the care of patients with diseases that can severely limit quality of life such as CSU, psoriasis, acne and atopic dermatitis. Advancing ligelizumab further strengthens the immuno-dermatology pipeline of Novartis. In the US, Novartis and Genentech, a member of the Roche Group, work together to develop and co-promote Xolair. Outside the US, Novartis markets Xolair and records all sales and related costs. Xolair is indicated as an add-on therapy for the treatment of CSU. Novartis is also testing remibrutinib (LOU064), a Bruton’s tyrosine kinase (BTK) inhibitor that is being tested in Phase II clinical studies for CSU11.

Disclaimer
This media update contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking etc. etc..

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References
1.Novartis. Data on file 2021.
2.Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria: A GA2LEN task force report. Allergy. 2011;66(3):317-330.
3.Vestergaard C, Deleuran M. Chronic spontaneous urticaria: latest developments in aetiology, diagnosis and therapy. Ther Adv Chronic Dis. 2015;6(6):304-313.
4.Ferrer M, Bartra J, Giménez?Arnau A, et al. Management of urticaria: not too complicated, not too simple. Clin Exp Allergy. 2015;45(4):731-743.
5.U.S. Food and Drug Administration (FDA). Frequently Asked Questions: Breakthrough Therapies. Available from: https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/frequently-asked-questions-breakthrough-therapies? [Last accessed: January 2021].
6.Puxeddu I, Pratesi F, Ribatti D, Migliorini P. Mediators of inflammation and angiogenesis in chronic spontaneous urticaria: Are they potential biomarkers of the disease? Mediators Inflamm. 2017;4123694.
7.Gasser P, Tarchevskaya SS, Guntern P, et al. The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab. Nat Commun. 2020;11(1):165.
8.Maurer M, Giménez-Arnau AM, Sussman G, et al. Ligelizumab for chronic spontaneous urticaria. N Engl J Med. 2019;381(14):1321-1332.
9.ClinicalTrials.gov. NCT03580369. A Phase III Study of the Efficacy and Safety of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled with H1-histamines [online] April 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03580369? [Last accessed: January 2021].
10.ClinicalTrials.gov. NCT03580356. A Phase III Study of the Efficacy and Safety of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled with H1-histamines [online] March 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03580356? [Last accessed: January 2021].
11.ClinicalTrials.gov. NCT03926611. Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines [online] December 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03926611? [Last accessed: January 2021].

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