Novartis’ Next-Gen Anti-IgE Antibody Ligelizumab Granted FDA Breakthrough Therapy Designation for Chronic Spontaneous Urticaria

January 14, 2021 News /BioonBIOON/ --Novartis(Novartis) recently announced that the U.S. Food and Drug Administration (FDA) has granted ligelizumab (QGE031) Breakthrough Therapy Designation for the treatment of patients with chronic spontaneous urticaria (CSU) who have an inadequate response to H1 antihistamine therapy.

It is worth mentioning that ligelizumab is the firstFDADrug Granted BTD for CSU Patients with Inadequate Response to H1 Antihistamines. Currently, treatment options for patients with CSU are limited. The BTD designation indicates that ligelizumab has the potential to provide substantial benefits over existing therapies.

Breakthrough Therapy Designation (BTD) is a new drug review pathway established by the FDA in 2012, aimed at accelerating the development and review of new drugs intended to treat serious or life-threatening diseases, where preliminary clinical evidence indicates that the drug demonstrates significant improvement over existing therapies on one or more clinically significant endpoints. Drugs granted BTD can receive, during their development, includingFDACloser guidance, including from senior officials, to ensure that new treatment options are made available to patients in the shortest possible time.

NovartisImmunologyAngelika Jahreis, MD, Global Head of Development for Hepatology and Dermatology, stated, “Chronic spontaneous urticaria is a debilitating disease that can significantly impact patients’ lives. Due to the limited treatment options available, patients are seeking more and better therapies to manage their condition.”FDABreakthrough Therapy designation, acknowledging the need for more effective treatments for this unpredictable, systemic, and debilitating disease.”

CSU (Image source: rappler.com）

Chronic Spontaneous Urticaria (CSU), also known as Chronic Idiopathic Urticaria (CIU), is an unpredictable and severe skin condition characterized by the appearance of urticaria (itchy, painful wheals), angioedema (swelling), or both, in the absence of specific external triggers. Due to its severity and unpredictability, CSU can be challenging or frustrating for patients. The condition typically persists for 1–5 years, but may last longer in some patients, negatively impacting quality of life. The pathogenesis of CSU is not yet fully understood, but it is currently known that most patients involveAutoimmunityMechanism.

Currently, chronic spontaneous urticaria (CSU) is treated with second-generation antihistamines. When high-dose antihistamine therapy fails, the anti-IgE monoclonal antibody Xolair (omalizumab) is typically added as a third-line treatment; nevertheless, many patients still fail to achieve complete symptom control.

Xolair, developed and marketed in collaboration by Novartis and Genentech (a member of the Roche Group), is a monoclonal antibody that targets and binds to IgE. Administered via subcutaneous injection, the drug was first approved in 2003 for the treatment of patients with symptoms that are difficult to control.AsthmaIn 2014, the drug was re-approved for the treatment of chronic spontaneous urticaria (CSU) refractory to H1 antihistamines. In the United States and Europe, Xolair has lost patent protection, currentlyNovartisActively advancing the clinical development of ligelizumab.

Mechanism of Action of Ligelizumab(Click the image to view a larger version)

Ligelizumab is a next-generation humanized anti-IgE monoclonal antibody that blocks the IgE/FcεR1 signaling pathway, a key driver of the inflammatory process in chronic spontaneous urticaria (CSU). Ligelizumab exhibits higher IgE affinity than Xolair and is currently in Phase III clinical development for the treatment of patients with CSU whose symptoms are not adequately controlled by H1 antihistamine therapy. The Phase III program comprises two Phase III clinical studies (PEARL 1 and PEARL 2), which have enrolled more than 2,000 patients across 48 countries worldwide.

In the Phase IIb dose-finding trial, a higher proportion of patients in the ligelizumab treatment group achieved complete resolution of wheals (urticaria) compared with the Xolair treatment group. In patients with chronic spontaneous urticaria (CSU) inadequately controlled by antihistamines, no safety concerns were identified with ligelizumab compared with Xolair or placebo.

Novartis is expected to launch in the United States in 2022FDASubmit the marketing application for ligelizumab. As a successor to Xolair, if ligelizumab is successfully launched, it will helpNovartisDefending the Exclusive Rights in the CSU Treatment Field. (Bioon.com)

Original Source: Novartis ligelizumab (QGE031) receivesFDA Breakthrough Therapy designation for patients with chronic spontaneous urticaria (CSU)