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Home Novartis Reports Phase III Results for Ligelizumab in Chronic Spontaneous Urticaria: Did Not Outperform Xolair

Novartis Reports Phase III Results for Ligelizumab in Chronic Spontaneous Urticaria: Did Not Outperform Xolair

Dec 21, 2021 01:46 CST Updated 01:46
Novartis

Drug Development and Manufacturing


CSU (Image Source: rappler.com）

News on December 20, 2021 /BioValleyBIOON/ --NovartisNovartis recently announced the top-line results of two Phase 3 studies (PEARL 1 and PEARL 2). These two studies are identically designed multicenter, randomized, double-blind, active drug and placebo-controlled, parallel-group studies conducted in over 2000 adult and adolescent (≥12 years) patients with chronic spontaneous urticaria (CSU) who had an inadequate response to H1 antihistamine treatment.Monoclonal Antibody DrugsEfficacy and Safety of Ligelizumab (QGE031) Compared to Placebo and Xolair (Omalizumab).

In two studies, patients were randomly assigned to receive ligelizumab 72mg, ligelizumab 120mg, Xolair 300mg, or placebo treatment once every four weeks for one year. Patients initially randomized to the placebo group switched to ligelizumab 120mg treatment from week 24 until the end of the 52-week treatment period. The primary endpoint was the change in the 7-day Urticaria Activity Score (UAS7) at week 12 relative to baseline.

The results showed that, in two studies:At Week 12 of treatment, ligelizumab demonstrated superiority over placebo in the primary endpoint but did not show superiority compared to Xoliris.

NovartisJohn Tsai, MD, Head of Global Drug Development and Chief Medical Officer at Novartis, stated: "We are disappointed that we were unable to demonstrate the superiority of ligelizumab over standard treatment in CSU. We will continue to evaluate the potential of ligelizumab to benefit patients with chronic inducible urticaria (CIndU) and food allergies, areas with significant unmet needs."

Novartis will release the full data of two studies after the research is completed in the second half of 2022. Recently,NovartisLaunchedremibrutinib(LOU064) Phase 3 study, the drugIt is a highly selective, potent, oral BTK inhibitor that has previously demonstrated rapid and effective CSU disease control.

CSU, also known as Chronic Idiopathic Urticaria (CIU), is an unpredictable and severe skin condition characterized by the appearance of hives (itchy, painful wheals), swelling (angioedema), or both, without specific external triggers. Due to its severity and unpredictability, CSU can be challenging or frustrating for patients. The condition typically lasts 1-5 years but may persist longer in some patients, negatively impacting their quality of life. The pathogenesis of CSU has not been fully elucidated, but it is currently known that most patients involveAutoimmunityMechanism.

CSU affects approximately 1% of the population, and about 60% of patients do not achieve full control of the condition with first-line antihistamine treatment. Currently, CSU is treated with second-generation antihistamine drugs.When high-dose antihistamine therapy fails, the anti-IgE monoclonal antibody Xolair (omalizumab) is typically added as a third-line treatment., even so, many patients still cannot fully control the symptoms.

XolairCo-developed and promoted by Novartis and Genentech, a subsidiary of Roche.Is a monoclonal antibody drug that targets and binds to IgE., administered via subcutaneous injection, was first approved in 2003 for the treatment of conditions that are difficult to control with symptoms.AsthmaThe patient was approved again in 2014 for chronic spontaneous urticaria (CSU) refractory to H1 antihistamines. In the United States and Europe, Xolair has lost patent protection and is currentlyNovartisActively promoting the clinical development of ligelizumab.

Mechanism of Action of Ligelizumab (Click image to enlarge)

Ligelizumab is a next-generation humanized anti-IgE monoclonal antibody that blocks the IgE/FcεR1 signaling pathway., which is a key driver of the CSU inflammatory process.Ligelizumab has a higher IgE affinity than Xolair., which is currently in Phase III clinical development for the treatment of CSU patients whose symptoms are not adequately controlled by H1 antihistamine therapy. The Phase III program for this drug includes two Phase III clinical trials (PEARL 1, PEARL 2), enrolling over 2000 patients across 48 countries worldwide.

In January 2021, the US FDA granted ligelizumab Breakthrough Therapy designation for the treatment of patients with chronic spontaneous urticaria (CSU) who have an inadequate response to H1 antihistamine therapy. Notably,Ligelizumab is the first to receiveFDADrug Granted BTD for CSU Patients with Inadequate Response to H1 AntihistaminesCurrently, treatment options for patients with CSU are limited. The BTD designation indicates that ligelizumab has the potential to offer substantial benefits over existing therapies.

In the Phase IIb dose-finding trial, a higher proportion of patients in the ligelizumab treatment group achieved complete resolution of hives (urticaria) compared to the Xolair treatment group. In patients with antihistamine-refractory CSU, no safety issues were identified with ligelizumab compared to Xolair or placebo.

Novartis had previously planned to launch in the United States in 2022FDASubmit the marketing application for ligelizumab. As the successor to Xolair, the successful launch of ligelizumab will helpNovartisDefend the exclusive rights in the CSU treatment field. (Bioon.com)