Novartis Receives Positive CHMP Opinion for Xolair (Omalizumab) as Add-on Therapy for Severe Chronic Rhinosinusitis with Nasal Polyps in the EU

June 28, 2020 News /BioValleyBIOON/ --Novartis(Novartis) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending approval of the anti-inflammatory drug Xolair (Chinese brand name: Zhuole; generic name: omalizumab) as an add-on therapy to intranasal corticosteroids (INC) for the treatment of adult patients (≥18 years) with severe chronic rhinosinusitis with nasal polyps (CRSwNP) whose disease is not adequately controlled with INC. CRSwNP is a chronic condition that often co-occurs with other respiratory diseases and causes a range of symptoms affecting patients’ quality of life, including loss of smell and nasal congestion.

The CHMP opinion will now be submitted to the European Commission (EC) for review, with a final decision expected within the next two months. If approved, Xolair would become the first therapy specifically targeting and blocking immunoglobulin E (IgE) for the treatment of nasal polyps, helping to reduce nasal polyp size (as defined by the Nasal Polyp Score [NPS]) and improve disease symptoms. Currently, the new indication application for Xolair in the treatment of CRSwNP is under review in several countries, including the United States and Switzerland.

Professor Philippe Gevaert from the Upper Airway Research Laboratory, Department of Otorhinolaryngology at Ghent University Hospital in Belgium, stated: “Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) experience persistent symptoms such as nasal congestion, facial pain, loss of smell and taste, difficulty breathing, and sleep disturbances, which significantly impair their quality of life. Unfortunately, despite receiving standard care and undergoing multiple sinus surgeries, many patients continue to experience symptoms. Xolair targets and blocks IgE, a key driver in the inflammatory pathway; if approved, this medication will provide a treatment option proven to significantly improve symptoms and quality of life for patients whose condition is not adequately controlled by INC.”

The CHMP’s positive opinion was based on the results of two Phase III clinical studies (POLYP 1 and POLYP 2). These were randomized, multicenter, double-blind, placebo-controlled, replicate Phase III studies evaluating the efficacy and safety of Xolair in adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who had an inadequate response to standard of care therapy (intranasal corticosteroids, INC). The POLYP 1 study enrolled 138 patients, and the POLYP 2 study enrolled 127 patients, including those with or without a history of surgery. In these studies, patients received subcutaneous injections of Xolair or placebo every 2–4 weeks, while continuing INC (mometasone furoate nasal spray) as background therapy. The co-primary endpoints for both studies were the change from baseline in Nasal Polyp Score (NPS) and the change from baseline in average daily Nasal Congestion Score (NCS) over 24 weeks of treatment.

The results of these two studies were published in June 2020 in "Allergy and Clinical"ImmunologyJournal of Allergy and Clinical Immunology (JACI). The data showed that both studies met their co-primary endpoints: compared with the placebo group, patients in the Xolair treatment group achieved statistically significant improvements in mean Nasal Polyp Score (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) at Week 24 of treatment. In both studies, patients in the Xolair treatment group demonstrated significant improvements in NPS and NCS as early as the first assessment (Week 4) compared with those in the placebo group.

Furthermore, two studies also met the key secondary endpoints: compared with the placebo group, patients in the Xolair treatment group showed improvements in health-related quality of life as assessed by the Sino-Nasal Outcome Test-22 (SNOT-22) scale, the University of Pennsylvania Smell Identification Test (UPSIT), the Total Nasal Symptom Score (TNSS), and olfaction; improvements were also observed in postnasal drip (posterior rhinorrhea) and runny nose (anterior rhinorrhea). In both studies, Xolair was well tolerated, and its safety profile was consistent with that observed in previous studies.

Linda Armstrong, M.D., Head of Respiratory Development at Novartis Pharmaceuticals, stated: “Novartis"The company’s mission is to reimagine and elevate the standard of care for patients with respiratory diseases by developing innovative therapies that alleviate disease symptoms and improve quality of life. This positive opinion from the CHMP builds upon Xolair’s established efficacy and safety profile, supported by more than 1.3 million patient-years of exposure, and positions it as a potential additional treatment option for patients with CRSwNP in the European Union."

Nasal Polyps (Image Source: myhealthandwellnessinfo.com)

Nasal polyps are a common and potentially debilitating condition with limited treatment options currently available. After standard care, surgery and systemic steroids remain the mainstay of treatment. However, due to the recurrence of nasal polyps, these approaches often fail to effectively control long-term chronic symptoms.

Nasal polyps present as non-cancerous lesions on the inner walls of the sinuses or nasal cavity, accompanied by irritation and inflammation, which can obstruct normal airflow. Nasal polyps frequently co-occur with other respiratory conditions, affecting approximately 45% of adults with episodicAsthmaIn patients, approximately 30% of those with chronic rhinosinusitis develop chronic rhinosinusitis with nasal polyps (CRSwNP) if symptoms of nasal polyps and sinusitis persist for 12 weeks or longer. After sinus surgery, the recurrence rate of nasal polyps is as high as 80%, and approximately 40% of patients require at least one additional surgical intervention. Around 80% of patients remain uncontrolled 3–5 years after sinus surgery.

It is worth noting that in June and October 2019, Sanofi and Regeneron’s anti-inflammatory drug Dupixent (dupilumab) was approved by the United States and the European Union for the treatment of adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP) whose condition was inadequately controlled. In the United States and the European Union, Dupixent is the first biologic therapy approved for the treatment of CRSwNP.

Xolair is the only approved anti-IgE antibody medication that specifically targets, binds to, and blocks IgE. By reducing free IgE levels, downregulating high-affinity IgE receptors, and limiting mast cell degranulation, Xolair minimizes the release of mediators during the allergic inflammatory cascade. This prescription drug is administered via subcutaneous injection and has been approved in multiple countries worldwide for the treatment of moderate-to-severe persistent allergicAsthma(SAA), chronic spontaneous urticaria (CSU), and chronic idiopathic urticaria (CIU). In addition, the Xolair pre-filled syringe has been approved for marketing in many countries worldwide. In the US market, the drug is jointly developed and promoted by Genentech, a member of the Roche Group, and Novartis; markets outside the United States are handled byNovartisResponsible for and record sales.

In China, Xolair (Chinese brand name: Zhuole; generic name: omalizumab) was approved in August 2017 for the treatment of patients aged 12 years and older with moderate-to-severe allergic asthma that is not adequately controlled by inhaled corticosteroids combined with long-acting β2-adrenergic receptor agonists. This approval makes Xolair (Zhuole) the first approved therapy in China for the treatmentAsthma's first targeted drug. (Bioon.com)

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