Novartis announces Xolair® approved in EU as first and only licensed therapy for chronic spontaneous urticaria patients unresponsive to antihistamines

Novartis announced today that the European Commission (EC) has approved the use of Xolair® (omalizumab) as an add-on therapy for the treatment of chronic spontaneous urticaria (CSU) in adult and adolescent (12 years and above) patients with inadequate response to H1-antihistamine treatment. The approved dose is 300 mg by subcutaneous injection every four weeks.

“The EU approval of Xolairin CSU is truly exciting for patients with this chronic and debilitating skin disease,” said David Epstein, Division Head of Novartis Pharmaceuticals. “With this new therapeutic option from our specialty dermatology portfolio, our aim is to help ensure that the up to 50% of patients who suffer from CSU and don’t respond to approved doses of antihistamines have access to Xolairas quickly as possible in the EU.”

At any given time, the prevalence of chronic urticaria (CU) is up to 1% of the world’s population⁵, and up to two thirds of these patients have CSU^5,6. 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 reoccur for more than six weeks^2-4. Up to 40% of CSU patients also experience angioedema, a swelling in the deep layers of the skin¹.

The EU approval follows the Committee for Medicinal Products for Human Use (CHMP) positive opinion on Xolair, which was adopted based on positive and consistent results from three pivotal Phase III registration studies (ASTERIA I, ASTERIA II and GLACIAL) that involved nearly 1,000 patients with CSU not responding to H1-antihistamines^7-9. Xolair 300 mg met all primary and pre-specified secondary endpoints across these studies, which showed Xolair significantly improved itch and hives, including rapid itch relief, and in many cases completely cleared symptoms^7-9. Quality of life was also significantly improved for patients treated with Xolair 300 mg^1-3 across the Phase III study program. Negative effects of CSU on quality of life may include sleep deprivation and psychological comorbidities such as depression and anxiety^5,10.

Results from the three pivotal registration studies for Xolair in CSU were announced in 2013. Highlights from these studies that were previously reported include:

In all three Phase III studies, a significant proportion of patients became either completely free of itch and hives (range 34-44%; p<0.001 to p<0.0001 at 300 mg) or had their symptoms suppressed to minimal levels (52-66%;p<0.0001 at 300mg)^7-9.

In the ASTERIA II study, 44% of patients receiving Xolair 300 mg were itch-and hive-free after 12 weeks of treatment (p<0.0001)⁹.

In the ASTERIA I study, Xolair-treated patients experienced a rapid reduction in itch and hives as early as Week 1, with the therapeutic benefit sustained over 24 weeks of active treatment (p<0.0001)⁷.

In the GLACIAL study, more than half of patients had failed multiple therapies including H1-antihistamines (at up to four times the approved dose) and H2-antihistamines and/or leukotriene receptor antagonists (LTRAs)⁸. Patient response in GLACIAL was similar to that seen in ASTERIA I and II, leading to elimination or suppression of symptoms to minimal levels within 2 weeks of the start of treatment, and sustained throughout the 24 week treatment period^7-9.

In the pivotal Phase III studies, the incidence and severity of adverse events (AEs) was similar between Xolair and placebo recipients^7-9.

In addition to the EU, Xolair has been approved for the treatment of CSU in five countries: Egypt, Turkey, Guatemala, El Salvador and Bangladesh. Regulatory reviews are currently ongoing in more than 20 countries, including the US, Canada, Australia and Switzerland.

Xolair is being jointly developed by Novartis and Genentech, Inc.

References

1. 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.
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. 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.
4. 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.
5. 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.
6. Kulthanan K, Jiamton S, Thumpimukvatana N, et al. Chronic idiopathic urticaria: prevalence and clinical course. J Dermatol. 2007;34:294-301.
7. Maurer M. Phase III randomized, double-blind, placebo-controlled study evaluating efficacy and safety of omalizumab in H1-antihistamine-refractory chronic idiopathic/spontaneous urticaria. European Academy of Dermatology and Venereology (EADV) annual meeting 2013. Oral Presentation. 5 October 2013, 11:30 a.m.
8. 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.
9. Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. NEJM. 2013; 368(10):924-35.
10. O’Donnell BF et al. The impact of chronic urticaria on the quality of life. Br J Dermatol. 1997; 136(2): 197-201.