Novartis receives positive CHMP opinion for new Xolair indication to treat severe chronic rhinosinusitis with nasal polyps

If approved, Xolair (omalizumab) will provide patients who have severe chronic rhinosinusitis with nasal polyps, not adequately controlled by intranasal corticosteroids, with the first anti-immunoglobulin E (IgE) antibody specifically designed to target and block IgE, a key driver in the inflammatory pathway

Decision based on results from the Phase III POLYP 1 and 2 studies, in which omalizumab* significantly reduced the size of nasal polyps (defined by Nasal Polyp Score) and improved nasal congestion (defined by Nasal Congestion Score) compared with placebo*1

Among secondary endpoints, omalizumab reduced post-nasal drip and runny nose, improved sense of smell, and patients reported an improvement in quality of life measures1

Omalizumab has a well-established safety record from over 1.3 million patient years of exposure and real-world evidence in severe allergic asthma and chronic spontaneous urticaria1

Basel, June 26, 2020 - Novartis today announced that the European Medicines Agency’s  Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Xolair (omalizumab) as an add-on therapy with intranasal corticosteroids (INC) for the treatment of adults (18 years and above) with severe chronic rhinosinusitis with nasal polyps (CRSwNP), for whom therapy with INC does not provide adequate disease control. If approved, omalizumab will be the first treatment for nasal polyps specifically targeting and blocking immunoglobulin E (IgE), which helps to reduce the size of nasal polyps (as defined by Nasal Polyps Score; NPS) and improve symptoms. The European Commission reviews the CHMP recommendation and usually delivers its final decision within two months.

"Patients with chronic rhinosinusitis with nasal polyps suffer from persistent symptoms, such as nasal congestion, facial pain, loss of sense of smell and taste, difficulty breathing and sleep problems, which can significantly impair their quality of life. Unfortunately, many patients continue to experience symptoms despite standard-of-care, and multiple sinus surgeries," said Professor Philippe Gevaert, Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium. "Omalizumab is specifically designed to block immunoglobulin E, which is a key driver in the inflammatory pathway; if approved, it will provide patients, for whom intranasal corticosteroids do not provide adequate disease control, with a treatment option that has been shown to improve both symptoms and quality of life."

The CHMP positive opinion is based on results from the Phase III POLYP 1 and 2 studies, which were published in the Journal of Allergy and Clinical Immunology in June 20201. These replicate studies demonstrated that patients treated with omalizumab achieved statistically significant improvements in mean NPS (POLYP 1: -1.08; p<0.0001, POLYP 2: -0.90; p=0.014) and daily Nasal Congestion Score (NCS; POLYP 1: -0.89; p=0.0004, POLYP 2: -0.70; p=0.0017) compared to placebo at Week 241 (co-primary endpoints). All patients received INC (mometasone nasal spray) as background therapy. In both studies, patients treated with omalizumab demonstrated significant improvements in NPS and NCS as early as first assessment (Week 4), compared to placebo1.

Among secondary endpoints, improvements were observed in the Sino-Nasal Outcome Test-22 (SNOT-22; a health-related quality of life assessment), the University of Pennsylvania Smell Identification Test (UPSIT), the Total Nasal Symptom Score (TNSS) and in sense of smell. Additionally, reductions in post-nasal drip (posterior rhinorrhea) and runny nose (anterior rhinorrhea) were seen1. In the studies, omalizumab was generally well tolerated and its safety profile was consistent with previous studies1.

"Novartis has a mission to reimagine and advance the care of respiratory patients by developing innovative treatment options that treat the disease, reduce symptoms and improve quality of life," said Linda Armstrong, MD, Respiratory Development Unit Head, Novartis Pharmaceuticals. "This CHMP positive opinion builds on the established efficacy and safety profile of omalizumab, which has over 1.3 million patient years of exposure and the potential to become an additional treatment option in the EU for patients with severe chronic rhinosinusitis with nasal polyps."

Novartis is committed to bringing omalizumab to patients with severe CRSwNP and additional regulatory filings are currently underway in multiple countries, including the US and Switzerland.

An injectable prescription medicine, Xolair is approved for the treatment of moderate-to-severe or severe persistent allergic asthma in more than 100 countries, including the US since 2003 and the EU since 2005. Xolair is approved for the treatment of chronic spontaneous urticaria in over 90 countries including the EU and for chronic idiopathic urticaria (CIU), as it is known in the US and Canada. Xolair has over 1.3 million patient years of exposure. In addition, a liquid formulation of Xolair in pre-filled syringes has been approved in the EU and in more than 20 countries outside of the EU, including Canada, the US, and Australia. The self-administration indication for Xolair in pre-filled syringes was also approved in the EU in 2018, and has since been approved in several other countries, including Australia, Taiwan, Argentina and Brazil. In the US, Novartis and Genentech, Inc. work together to develop and co-promote Xolair. Outside of the US, Novartis markets Xolair and records all sales and related costs.

If approved, Xolair will be indicated as an add-on therapy with intranasal corticosteroids (INC) for the treatment of adults (18 years and above) with severe chronic rhinosinusitis with nasal polyps, for whom therapy with INC does not provide adequate disease control; the first approval in the world for omalizumab in this indication.

About POLYP 1 and POLYP 21
POLYP 1 and POLYP 2 are replicate Phase III studies designed to determine the efficacy and safety of omalizumab compared with placebo in adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who have had an inadequate response to daily intranasal corticosteroid (INC) therapy. All patients received INC (mometasone nasal spray) as background therapy. Both trials were randomized, multicenter, double-blind and placebo-controlled. POLYP 1 involved 138 patients and POLYP 2 involved 127 patients, with and without a history of surgery or prior use of systemic corticosteroids. The co-primary endpoints for both trials were change from baseline in average daily Nasal Congestion Score (NCS), and change from baseline in Nasal Polyp Score (NPS) at Week 24. Patients in the studies were administered either omalizumab or placebo by subcutaneous injection every 2-4 weeks.

Secondary endpoints included change from baseline at Week 24 in Sino-Nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test (UPSIT), mean daily sense of smell, post-nasal drip, runny nose, and Total Nasal Symptom Score (TNSS); change from baseline at Week 16 in NPS and NCS; and percentage of patients requiring rescue therapy (systemic corticosteroids for

=3 consecutive days and/or nasal polypectomy) by Week 24. Reduction in need for surgery through Week 24 was predefined as patients achieving NPS of

=8.9 points) in SNOT-22. The percentage of patients with comorbid asthma demonstrating minimal clinically important difference improvement (

=0.5 points) in Asthma Quality of Life Questionnaire (AQLQ) through Week 24 was also assessed.

Exploratory endpoints included percentage of patients in the pooled population achieving =1-point improvement in NCS. Adverse events (AEs) were assessed for severity and potential causal relationship to the study drug. Patients were monitored to Week 28 as safety follow-up.

About Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
Chronic rhinosinusitis with nasal polyps (CRSwNP) impacts up to 4% of people worldwide. It is a potentially debilitating condition in adults that is characterized by inflammation of the nose and paranasal sinuses with the presence of benign inflammatory polyps (nasal polyps) on the lining of the nasal sinuses or nasal cavity, which can block normal airflow2-4. It is possible to have a single polyp or several, and the size of the polyps can vary from microscopic to several centimeters5,6.

Symptoms can include nasal blockage/obstruction, nasal congestion, nasal discharge, facial pain/pressure and reduction in, or loss of, sense of smell2,3. CRSwNP is diagnosed by physical examination with endoscopy. The condition can be associated with asthma, cystic fibrosis and aspirin sensitivity7. It is also associated with significant morbidity and decreased health-related quality of life, with quality of life impairment8-13. Patients with CRSwNP experience significantly lower health-related quality of life than the general population, with a greater impact for patients with more severe disease, other conditions (comorbidities), or whose CRSwNP has not responded to treatment (refractory disease)11.

Currently, after standard-of-care, surgery and systemic steroids are the main treatments for this disease all over the world. Many patients choose them; however, they are often not effective in controlling chronic symptoms over time, due to nasal polyps regrowth. After sinus surgery, nasal polyps recur in up to 80% of people, with approximately 40% requiring at least one additional surgery8. Approximately 80% of people remain uncontrolled 3-5 years after sinus surgery14.

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