Three clinical trials announced for Fasenra in eosinophil-driven skin diseases
Fasenra being evaluated in eight eosinophil-driven diseases beyond severe asthma
AstraZeneca today announced three new trials for Fasenra (benralizumab) in skin diseases, adding to five trials already underway for the medicine in eosinophil-driven diseases (EDDs) beyond severe asthma.
In EDD, immune system dysfunction causes eosinophil recruitment and activation leading to chronic local and/or systemic inflammation.1
The three new trials for Fasenra in skin diseases include two Phase II trials to assess the potential of the medicine in atopic dermatitis (AD) and chronic spontaneous urticaria (CSU); and a Phase III trial in bullous pemphigoid (BP).
Five additional Phase III clinical trials are underway to investigate the potential of Fasenra in:
|Disease||Trial name||Estimated data readout|
|Chronic obstructive pulmonary disease (COPD)||RESOLUTE: Efficacy and safety of benralizumab in moderate to very severe COPD with a history of frequent exacerbations2||2023|
|Eosinophilic esophagitis (EoE)||MESSINA: Efficacy and safety of benralizumab in patients with EoE3||2023|
|Eosinophilic granulomatosis with polyangiitis (EGPA)||MANDARA: A study to evaluate if benralizumab compared to mepolizumab may be beneficial in the treatment of EGPA4||2023|
|Hypereosinophilic syndrome (HES)||NATRON: A phase 3 study to evaluate the efficacy and safety of benralizumab in patients with HES5||2023|
|Nasal polyposis (NP)||OSTRO: Efficacy and safety study of benralizumab for patients with severe nasal polyposis6||
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “These clinical trials represent significant progress towards our ambition to establish Fasenra as the first-line, first-choice treatment for patients with eosinophil-driven diseases, which can be debilitating and potentially life-threatening. I’m proud of the rapid progress we’re making to evaluate Fasenra in these diseases where patients today have limited or no approved treatment options.”
Fasenra is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries and is approved for self-administration in the US and EU. The US Food and Drug Administration granted Orphan Drug Designation for Fasenra for EGPA (November 2018), HES (February 2019) and EoE (August 2019).
Also known as eczema, AD is a chronic disease that causes the skin to become inflamed and irritated, which for many patients can be painful and lead to emotional stress and infections.7
Half of patients with moderate to severe eczema also suffer from asthma, hay fever (allergic rhinitis), and food allergies.7
Current treatments seek to clear skin inflammation and itching and improve quality of life, and often include topical creams and lotions, antihistamines, topical and oral steroids and biologic medicines that can help to reduce inflammation.7
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.8
CSU has a significant burden on patients’ quality of life including sleep impairments and overall functioning.9 Initial treatment approaches include the use of antihistamines. This approach fails to resolve symptoms in more than half of all CSU patients, nearly 45 percent of whom have CSU associated with autoimmunity,10 and other treatment methods must be considered. When antihistamines are unsuccessful, patients are often treated with corticosteroids, cyclosporine and the FDA-approved biologic omalizumab.10
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 old.11
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. These include: antibacterial ointments to prevent infection, topical and oral corticosteroids, anti-inflammatory antibiotics, and in more severe cases, immunosuppressants.11
COPD is a progressive disease which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness.12 It affects an estimated 384 million people worldwide and is predicted to be the third leading cause of death by 2020.12 Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important treatment goals in the management of COPD.12
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.13 COPD exacerbations significantly impair quality of life and are linked to disease progression, accelerated decline in lung function, and increased hospitalisations and mortality.14,15,16
Elevated blood eosinophil counts for patients with COPD are associated with increased exacerbation risk and increased responsiveness to inhaled corticosteroid treatment.17
EoE is a rare, chronic, inflammatory disease of the oesophagus 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.18
The most common symptoms of EoE include reflux that does not respond to medication, difficulty swallowing, food becoming stuck in the oesophagus, nausea and vomiting, abdominal or chest pain, poor appetite and difficulty sleeping.18
Patients are often treated with corticosteroids to manage inflammation. Currently there are no FDA-approved treatments for EoE.18
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.19 EGPA can result in damage to multiple organs, including lungs, skin, heart, gastrointestinal tract and nerves.20 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.19,20,21 Without treatment, the disease may be fatal.20
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.19,20 People with EGPA usually have asthma that may have developed as an adult, and often have sinus and nasal symptoms.19
There are few effective medicines for EGPA. Patients are often treated with chronic high-dose oral corticosteroids (OCS) and can experience recurrent relapses when attempting to taper off OCS.19,22 Mepolizumab is currently the only approved biologic medicine for EGPA.
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.23,24 HES most commonly impacts the skin, heart, lungs, gastrointestinal tract and central nervous system.24
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.24
The goal of HES treatment is to reduce eosinophils in the blood and tissues, prevent organ damage and slow disease progression.24,25 HES treatment typically includes glucocorticoids, immunomodulatory therapies and cytotoxic therapies.23
Nasal polyps are growths on the lining of the sinuses and nasal passages. In patients with NP, elevated levels of eosinophils accumulate in the upper respiratory tract. Nasal polyps can develop when the mucous membrane of the nasal passages and sinuses are inflamed, typically for 12 weeks or more. Some of these growths can be large enough to block the nasal passages. When this occurs, it can lead to breathing problems, frequent sinus infections or loss of ability to smell.26
Nasal polyps are often associated with respiratory diseases such as allergic rhinitis, rhinosinusitis (chronic sinusitis), asthma or cystic fibrosis.26
Current treatments include intranasal or oral corticosteroids (OCS) and surgery to remove polyps, but these often do not address the underlying cause of the disease. Dupilumab is currently the only biologic approved to treat NP.26
Fasenra 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 eosinophils via apoptosis (programmed cell death).27,28
Fasenra is AstraZeneca’s first respiratory biologic, now approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries, with further regulatory reviews ongoing. In the US, Fasenra is approved for self-administration in the Fasenra Pen. In the EU, Fasenra is approved for self-administration in either the single-use, pre-filled syringe or the Fasenra Pen.
Fasenra was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.
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