First patients dosed in Phase III trials evaluating Fasenra in hypereosinophilic syndrome, eosinophilic esophagitis and eosinophilic granulomatosis with polyangiitis

New clinical trial also announced for Fasenra

in eosinophilic gastritis/eosinophilic gastroenteritis

The first patients have been dosed in Fasenra (benralizumab) Phase III trials in three rare eosinophilic diseases: hypereosinophilic syndrome (HES), eosinophilic esophagitis (EoE) and eosinophilic granulomatosis with polyangiitis (EGPA)

AstraZeneca will also initiate a Phase III trial to investigate the potential of Fasenra in an additional rare eosinophilic disease: eosinophilic gastritis/eosinophilic gastroenteritis (EG/EGE). This trial extends the Fasenra clinical programme to nine diseases where eosinophils play an important role, in addition to severe asthma.

In eosinophil-driven diseases, abnormal responses in the immune system causes the recruitment and activation of eosinophils, leading to chronic local and/or systemic inflammation that can drive or worsen disease across a range of tissues or organ systems throughout the body.¹ These diseases can result in a range of debilitating symptoms and have limited treatment options. 

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “This new Phase III trial for Fasenra in another rare eosinophil-driven disease represents an important advancement of our clinical development programme, with the ultimate goal of improving patients’ outcomes. Based on its eosinophil-depleting mechanism of action, we hope that Fasenra can help address the underlying causes of eosinophilic-driven diseases and the limited treatment options for patients today.”

Fasenra is being investigated in the following 10 trials, including four rare diseases which are defined by the Food and Drug Administration (FDA) as those affecting fewer than 200,000 people in the US.²

 

Disease	Trial name	Estimated data readout
Atopic dermatitis (AD)	HILLIER: A phase II trial to evaluate the efficacy and safety of benralizumab in moderate to severe AD3	Data anticipated 2021+
Bullous pemphigoid (BP)	FJORD: A phase III trial to evaluate the efficacy and safety of benralizumab in patients with BP4	Data anticipated 2021+
Chronic obstructive pulmonary disease (COPD)	RESOLUTE: A phase III trial to evaluate the efficacy and safety of benralizumab in patients with moderate to very severe COPD with a history of frequent exacerbations5	Data anticipated 2021+
Chronic rhinosinusitis with nasal polyps (CRSwNP)	OSTRO: A Phase III trial to evaluate the efficacy and safety study of benralizumab in patients with severe nasal polyposis6 ORCHID: A Phase III trial to evaluate the efficacy and safety study of benralizumab in patients with eosinophilic CRSwNP7	Completed     Data anticipated 2021+
Chronic spontaneous urticaria (CSU)	ARROYO: A phase II trial to evaluate the efficacy and safety of benralizumab in patients with moderate to severe CSU8	Data anticipated 2021+
Eosinophilic esophagitis (EoE)	MESSINA: A phase III trial to evaluate the efficacy and safety of benralizumab in patients with EoE9	Data anticipated 2021+
Eosinophilic gastritis/ Eosinophilic gastroenteritis (EG/EGE)	HUDSON: A phase III trial to evaluate the efficacy and safety of benralizumab in patients with EG/EGE10	Data anticipated 2021+
Eosinophilic granulomatosis with polyangiitis (EGPA)	MANDARA: A phase III trial to evaluate if benralizumab compared to mepolizumab may be beneficial in the treatment of EGPA11	Data anticipated 2021+
Hypereosinophilic syndrome (HES)	NATRON: A phase III trial to evaluate the efficacy and safety of benralizumab in patients with HES12	Data anticipated 2021+

 

Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries¹³ and is approved for self-administration in the US¹⁴ and EU.¹⁵ The FDA granted Orphan Drug Designation for Fasenra for EGPA (November 2018),¹⁶ HES (February 2019)¹⁷ and EoE (August 2019).¹⁸

 

AD

Also known as eczema, AD is a chronic disease that causes the skin to become inflamed, irritated, and itchy, which for many patients can be painful and lead to emotional stress and infections.¹⁹ Half of patients with moderate to severe eczema also suffer from asthma, hay fever (allergic rhinitis), and food allergies.¹⁹ AD is associated with elevated levels of eosinophils in most patients, and there is a suggestion that higher levels correlate with disease activity.²⁰

 

Current treatments seek to clear skin inflammation and itching, improve quality of life, and often include topical creams and lotions, antihistamines, topical and oral corticosteroids (OCS) and biologic medicines that can help to reduce inflammation.²⁰

 

BP

BP is a rare, autoimmune, chronic skin disorder characterised by blistering, urticarial lesions (hives) and itching. The disorder typically occurs in elderly patients with an average patient age of 80 years.²¹ Eosinophilic infiltration in the skin is a prominent feature of BP and believed to contribute to the itching and skin blistering observed.²²

 

There are currently no therapies specifically approved for BP, however certain medicines can reduce itching and formation of new blisters, but do not address underlying causes of the disease. The most commonly used treatments are topical and OCS, which are poorly tolerated in the elderly population.²²

 

COPD

COPD is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness.²³ It affects an estimated 384 million people worldwide²⁴ and is predicted to be the third leading cause of death by 2020.²⁵ Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important treatment goals in the management of COPD.²³

 

An estimated 40% of moderate to severe COPD patients on triple inhaled therapy - inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) - remain uncontrolled and continue to experience exacerbations.²⁶ COPD exacerbations, which can significantly impair quality of life and are linked to disease progression, accelerate decline in lung function, and increase hospitalisations and mortality.^27-30

 

CRSwNP

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by persistent inflammation of the mucous membrane lining the nasal passages and sinuses accompanied by benign growths, called nasal polyps.^31,32 Nasal polyps can block nasal passages and lead to breathing problems, reduction in the sense of smell, nasal discharge, sleep disturbance and other adverse effects on quality of life.^33-35 The disease is associated with elevated levels of eosinophils accumulating in the upper respiratory tract.³⁶

 

Current treatments for nasal polyps include intranasal or OCS and surgery to remove polyps, but these often do not address the underlying cause of the disease and the need for repeated interventions can be high.^37,38 Since 2019, other biologic medicines have been approved or recommended to treat nasal polyps.^34,39

 

CSU

CSU is a dermatological condition where hives, welts, or swelling under the skin form on the skin and last for more than six weeks. Hives are itchy and can occur anywhere on the body including the face, extremities, chest, back or face. Hives range in size from just a few millimetres to several centimetres.⁴⁰ Eosinophil infiltration and activation play a role in CSU disease pathophysiology.⁴¹

 

CSU has a significant burden on patients’ quality of life including sleep impairments and overall functioning.⁴² Initial treatment approaches include the use of antihistamines. This approach fails to resolve symptoms in more than half of all CSU patients,⁴³ and other treatment methods must be considered. When antihistamines are unsuccessful, patients are often treated with corticosteroids, cyclosporine and the FDA-approved biologic omalizumab.⁴³

 

EoE

EoE is a rare, chronic, inflammatory disease of the esophagus characterised by the accumulation of eosinophils in the esophageal lining tissue. The disease results in injury, fibrosis and dysfunction that if not effectively treated can make eating difficult or uncomfortable, potentially leading to chronic pain, difficulty swallowing, poor growth, malnutrition and weight loss.⁴⁴

 

Patients also find it necessary to significantly modify their diet and eating behaviors to manage the symptoms of the disease. Currently there are no FDA-approved treatments for EoE.⁴⁴

 

EG/EGE

EG/EGE are rare, chronic, relapsing diseases characterised by inflammation of the stomach and/or small bowel, which result in a variety of non-specific, debilitating gastrointestinal symptoms such as abdominal pain, nausea, vomiting, satiety (feeling overfull), loss of appetite, and diarrhoea.^45-48 EG/EGE symptoms are primarily related to eosinophilic inflammation, which causes tissue injury and remodelling of the stomach and small bowel lining.⁴⁹

 

There are no approved treatments.⁴⁸ Disease management includes strict dietary changes with more severe patients receiving locally acting or OCS.^45-47

 

EGPA

EGPA, formerly known as Churg-Strauss Syndrome, is a rare, chronic autoimmune disease that is caused by inflammation of small to medium-sized blood vessels.⁵⁰ EGPA can result in damage to multiple organs, including lungs, skin, heart, gastrointestinal tract and nerves.⁵¹ The most common symptoms and signs include extreme fatigue, weight loss, muscle and joint pain, rashes, nerve pain, sinus and nasal symptoms, and shortness of breath.^50-52 Without treatment, the disease may be fatal.⁵¹

 

Elevated levels of eosinophils play a central role in EGPA disease pathophysiology. All patients with EGPA have very high levels of eosinophils at some point in their disease, both in peripheral blood and in affected tissues or organs.^50,51 People with EGPA usually have asthma that may have developed as an adult, and often have sinus and nasal symptoms.⁵⁰

 

There are few effective medicines for EGPA. Patients are often treated with chronic high-dose OCS and can experience recurrent relapses when attempting to taper off OCS.^50,53 Mepolizumab is currently the only approved biologic medicine for EGPA.⁵⁴

 

HES

HES is a group of rare disorders in which high numbers of eosinophils are found in the blood and tissue that can cause progressive organ damage over time, and if left untreated, can be fatal.^55,56 HES most commonly impacts the skin, heart, lungs, gastrointestinal tract and central nervous system.⁵⁶

 

The symptoms of HES may include cough, fever, fatigue, asthma, difficulty breathing, wheezing, recurrent upper respiratory tract infections, abdominal pain, vomiting, diarrhoea, skin rashes, arthritis, muscle aches and joint pain.⁵⁶

 

The goal of HES treatment is to reduce eosinophils in the blood and tissues, prevent organ damage and slow disease progression.^56,57 HES treatment typically includes glucocorticoids, immunomodulatory therapies and cytotoxic therapies.⁵⁵

 

Fasenra

Fasenra (benralizumab) is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of blood and tissue eosinophils in most patients via apoptosis (programmed cell death).^58,59

 

Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries,¹³ and is approved for self-administration in the US,¹⁴ EU¹⁵ and other countries.

 

Fasenra is in development for other eosinophilic diseases and chronic obstructive pulmonary disease. The US Food and Drug Administration granted Orphan Drug Designation for Fasenra

for EGPA (November 2018),¹⁶ HES (February 2019)¹⁷ and EoE (August 2019).¹⁸

 

Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

 

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology is one of AstraZeneca’s three therapy areas and is a key growth driver for the Company.

 

Building on a 50-year heritage, AstraZeneca is an established leader in respiratory care across inhaled and biologic medicines. AstraZeneca aims to transform the treatment of asthma and chronic obstructive pulmonary disease (COPD) by eliminating preventable asthma attacks across all severities and removing COPD as leading cause of death through earlier, biology-led treatment. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell repair processes in disease and neuronal dysfunction.

 

With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immune-driven diseases. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential in rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology and systemic eosinophilic-driven diseases. AstraZeneca’s ambition in immunology is to achieve disease control and ultimately clinical remission in targeted immune-driven diseases.

 

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

 

Contacts

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