AstraZeneca's Fasenra (Benralizumab) Achieves Positive Phase III Results in Chronic Rhinosinusitis with Nasal Polyps

September 11, 2020 /BioValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced that the novel anti-inflammatory drug Fasenra (benralizumab) in the Phase III OSTRO trial for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP)simultaneously achieved the co-primary endpoints of reducing nasal polyp size and alleviating obstruction。

CRSwNP is a chronic disease that often co-occurs with other respiratory conditions, severely impairing patients' quality of life. Its symptoms include: chronic nasal congestion, difficulty breathing and sleeping, and loss of smell. OSTRO is a study of Fasenra for the treatment of CRSwNP.Clinical Trialpart of the project, which also includes the ongoing Phase III ORCHID trial, among others.

OSTRO is a randomized, double-blind, multicenter, parallel-group, 56-week Phase III trial evaluating the efficacy and safety of Fasenra versus placebo in patients with nasal polyps. The study enrolled 413 patients from Europe and North America, regardless of blood eosinophil count or presence of comorbiditiesAsthma. These patients remained symptomatic despite receiving standard of care (SoC) treatment. SoC included intranasal corticosteroids (INCS), prior surgery, and/or the use of systemic corticosteroids. In the study, patients were randomized to receive subcutaneous injections of Fasenra 30 mg or placebo every 4 weeks for the first three doses, and thereafter every 8 weeks.The primary endpoints were: (1) the effect of Fasenra on nasal polyp burden compared with placebo at Week 40, as assessed by the change in total Nasal Polyp Score (NPS) via nasal endoscopy; and (2) the effect of Fasenra on patient-reported nasal congestion compared with placebo at Week 40, as assessed by the change in the mean Nasal Blockage Score (NBS).

Nasal Polyps (Image source: myhealthandwellnessinfo.com)

High-level results from the study showed that in patients with chronic rhinosinusitis with nasal polyps (CRSwNP),Compared with placebo, Fasenra treatment resulted in statistically significant improvements in nasal polyp size and nasal obstruction.In patients with severe bilateral nasal polyps who remained symptomatic despite continued standard-of-care (SoC) treatment, Fasenra demonstrated statistically significant improvements in the total Nasal Polyp Score (NPS) and Nasal Blockage Score (NBS) compared with placebo. The safety and tolerability profile of Fasenra in this study was consistent with its known drug characteristics.

Professor Claus Bachert, Principal Investigator of the study, Head of the Department of Otorhinolaryngology at Ghent University Hospital in Belgium, and Director of the Upper Airway Research Laboratory, stated, “CRSwNP is difficult to treat, and the underlying drivers and natural history of the disease are not yet fully understood. The results of the OSTRO study indicate that”The eosinophil depletion mechanism of Fasenra may bring therapeutic benefits to patients suffering from this disease.。”

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated: “Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) suffer from severe nasal congestion and reduced quality of life. Current treatments, such as intranasal or oral corticosteroids and surgical polypectomy, do not fully meet patient needs. Data from the OSTRO study indicate that Fasenra can benefit patients with nasal polyps. We look forward to completing the full analysis and presenting it at upcoming medicalMeetingshare these results above.”

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is characterized by persistent inflammation of the nasal and sinus mucosa accompanied by benign growths known as nasal polyps. Nasal polyps can obstruct the nasal passages, leading to breathing difficulties, reduced sense of smell, decreased nasal secretions, sleep disturbances, and other adverse effects on quality of life. This condition is associated with elevated levels of eosinophils, a type of white blood cell that accumulates in the upper respiratory tract.

Currently, treatment options for nasal polyps include intranasal or oral corticosteroids (OCS) and surgical removal of nasal polyps; however, these approaches often fail to address the underlying cause of the disease, thereby necessitating repeated interventions. Since 2019, several other biologic agents have been approved or recommended for the treatment of nasal polyps.

June 2019, Sanofi and Regeneron's anti-inflammatory drugDupixent (Chinese brand name: Dabito, generic name: dupilumab)approved for market launch, becoming the first biologic therapy approved for the treatment of CRSwNP. In August 2020,NovartisAnti-inflammatory drugsXolair (Chinese brand name: Zhuole; generic name: omalizumab)Approved as the first therapy specifically targeting and blocking immunoglobulin E (IgE) for the treatment of CRSwNP.

Image source: vasculitides.com

Fasenra (benralizumab)The active pharmaceutical ingredient is benralizumab, a monoclonal antibody that directly binds to the alpha subunit of the interleukin-5 receptor (IL-5Rα) on eosinophils and uniquely recruits natural killer (NK) cells, throughApoptosis(Programmed cell death) induces rapid and nearly complete depletion of eosinophils.

Fasenra is AstraZeneca’s first respiratory biologic, approved in the United States, the European Union, Japan, and several other countries as an add-on maintenance therapy for severe eosinophilicAsthmaTreatment of patients. Currently, Fasenra is also being evaluated for its potential in treating severe nasal polyps, eosinophilic esophagitis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, and chronic obstructive pulmonary disease.

It is worth mentioning that in April this year,GlaxoSmithKlineanti-inflammatory drugsNucala (mepolizumab, Mepolizumab)The pivotal Phase III SYNAPSE study yielded positive results, marking the first time a Phase III trial of an anti-IL-5 biologic has reported positive data in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP). Nucala is the first IL-5-targeted biologic therapy approved globally. IL-5 is a cytokine that regulates the growth, activation, and survival of eosinophils (a type of white blood cell) and provides critical signals for their migration from the bone marrow to the lungs and other organs. Nucala binds to human IL-5, thereby blocking its interaction with receptors on the surface of eosinophils. By inhibiting this binding, Nucala reduces eosinophil levels in the blood, tissues, and sputum, which in turn diminishes eosinophil-mediated inflammation. (Bioon.com)

Original Source: Fasenra met both co-primary endpoints of reduced nasal polyp size and blockage in the OSTRO Phase III trial for patients with chronic rhinosinusitis with nasal polyps