Xolair Demonstrates Significant Efficacy in Two Pivotal Phase III Trials for Chronic Rhinosinusitis with Nasal Polyps

Roche and Novartis recently announced positive topline data from two Phase III studies (POLYP 1 and POLYP 2) evaluating the anti-inflammatory drug Xolair (omalizumab) for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). These two studies were randomized, multicenter, double-blind, placebo-controlled, replicate Phase III trials designed to assess the efficacy and safety of Xolair in adult patients with CRSwNP who had an inadequate response to standard of care therapy (intranasal corticosteroids).

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. The co-primary endpoints were both the change from baseline in Nasal Polyp Score (NPS) and the change from baseline in mean daily Nasal Congestion Score (NCS) over 24 weeks of treatment.

The results showed that both studies met the co-primary endpoints: compared with the placebo group, patients in the Xolair treatment group demonstrated statistically significant and clinically relevant improvements from baseline in NPS and NCS over 24 weeks of treatment. Furthermore, the studies also met key secondary endpoints, including improvement in olfaction, postnasal drip (posterior rhinorrhea score), rhinorrhea (anterior rhinorrhea score), and health-related quality of life as assessed by the Sino-Nasal Outcome Test-22 (SNOT-22). Xolair was well tolerated in the studies, with a safety profile consistent with previous findings in patients treated for moderate-to-severe allergic asthma and chronic idiopathic urticaria.

Detailed data from these two studies will be presented at an upcoming scientific conference. Dr. Sandra Horning, Chief Medical Officer and Head of Global Product Development at Roche, stated, “The results of these pivotal studies further support the role of IgE in inflammatory and respiratory diseases and demonstrate that Xolair reduces nasal polyp size and associated symptoms that impact patients’ quality of life. We plan to discuss these findings with the FDA with the aim of bringing this new treatment option as soon as possible to patients who have not achieved disease remission with current standards of care.”

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nasal and paranasal sinus mucosa. As a heterogeneous condition, CRS is classified into two phenotypes based on the presence or absence of nasal polyps: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP is characterized by the presence of polyps obstructing the sinuses and nasal passages. Due to its more severe symptoms and higher postoperative recurrence rate, CRSwNP has become a focal point of clinical research. Current treatment options for CRSwNP include intranasal corticosteroids, systemic corticosteroids, and surgery; however, these therapies often yield suboptimal efficacy and/or high recurrence rates. Patients may experience severe nasal obstruction, breathing difficulties, rhinorrhea, reduced or lost sense of smell and taste, and facial pain or pressure. The persistent symptoms of CRSwNP significantly adversely affect patients’ health-related quality of life, leading to reduced productivity and impairment in activities of daily living, inability to enjoy food, sleep deprivation, and fatigue.

Xolair is the only approved antibody drug that targets, binds to, and blocks immunoglobulin E (IgE). By reducing free IgE levels, downregulating high-affinity IgE receptors, and limiting mast cell degranulation, it minimizes the release of mediators in the allergic inflammatory cascade. This prescription injectable medication has been approved in numerous countries worldwide for the treatment of moderate-to-severe persistent allergic asthma, chronic spontaneous urticaria (CSU), and chronic idiopathic urticaria (CIU). In 2018, global sales of Xolair approached $3 billion. In the US market, the drug is co-developed and co-promoted by Genentech, a member of the Roche Group, and Novartis; outside the United States, Novartis is responsible for commercialization and records sales. Currently, both parties are evaluating Xolair for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP).

Currently, there are no biologic therapies approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). Notably, in March this year, the U.S. Food and Drug Administration (FDA) granted priority review to the supplemental biologics license application submitted by Sanofi and Regeneron for Dupixent, a novel anti-inflammatory agent, for the treatment of CRSwNP. A regulatory decision is expected by the end of this month. If approved, Dupixent will become the first biologic agent indicated for CRSwNP. Dupixent is a fully human monoclonal antibody that specifically inhibits the overactivated signaling of two key proteins, interleukin-4 (IL-4) and interleukin-13 (IL-13). IL-4 and IL-13 are inflammatory cytokines considered to be key drivers of underlying inflammation in allergic diseases and other type 2 inflammatory conditions, including CRSwNP, atopic dermatitis, asthma, and eosinophilic esophagitis.

References:

1.Xolair (omalizumab) significantly reduced nasal polyps and congestion symptoms in adults with chronic rhinosinusitis with nasal polyps in two phase III studies

2.https://www.roche.com/investors/updates/inv-update-2019-06-03b.htm