IEBS - breathe-easier-with-astrazeneca-fasenra

Chronic obstructive pulmonary disease, or COPD, is a chronic inflammatory disease that causes a cough with mucus, wheezing, shortness of breath or chest tightness, all of which make breathing difficult.

COPD is a progressive disease which develops gradually and typically winds up evident following 40 years of age. An individual suffering from COPD experiences exacerbation episodes frequently, in which the symptoms become worse and persist for several days and could be seriously disabling and may result in the need for urgent medical attention.

COPD is diagnosed by spirometry, which measures lung function i.e. a measure of air an individual can inhale and speed of air that can move into and out of the lungs.[1]

Symptoms are most evident when significant lung damage has already occurred, and usually worsen with time. Although COPD has no cure, proper medication and lifestyle changes can reduce some of its symptoms and the progression of disease could be delayed.[2]

It has been assessed that 329 million individuals which are roughly 4.77% of the total population is affected by COPD and is anticipated to turn into the third-driving reason for death worldwide by 2020.[3]

COPD symptoms can get worse quickly if not treated or treated correctly. Pulmonary rehabilitation, reducing risk factors such as smoking, in-door & out-door pollution, drugs such as bronchodilators, corticosteroids and long-term antibiotics, supplemental oxygen and lung transplantation or lung-volume-reduction surgery are the treatment options available for mild to severe COPD. [4]

One of the most well-founded treatment includes Benralizumab, which is a humanized monoclonal antibody developed by AstraZeneca and its global biologics research and development arm MedImmune under the trade name Fasenra, for the treatment of moderate to severe COPD. It is approved as an add-on therapeutics for severe eosinophilic asthma in US, EU, Japan, and several other countries.

Benralizumab binds with alpha chain of human interleukin-5 receptor (CD125), which brings about hindrance of IL5-intervened receptor activation. It targets the circulating effector cells and eosinophils resident in the lung tissue. It also induces the depletion of circulating eosinophils in a rapid manner, with an onset of action of 24 hours as confirmed in phase 1 and phase 2 severe asthma trials, as indicated by AstraZeneca.[5]

Benralizumab failed to live up to the expectations in the phase 3 clinical trials named Galathea.[6] The company declared in a public statement that, there has not been a statistically appreciable reduction in exacerbations of patients with COPD in the late stages of trial and missed its primary endpoint. However, AstraZeneca said that the safety and tolerability findings in the phase 3 trials were consistent as compared with previous trials.[7]

To determine the future advancement of Benralizumab for COPD, a separate study with the identical number of patients, named Terranova, is ongoing, and AstraZeneca said it would assess the two trials to determine the succeeding steps for Fasenra in COPD.[8]

Increasing occurrence of COPD in general populace is a condition of stress, keeping in mind that the hazard factors related with the malady stayed same or even declined in few developing nations attributable to indoor air contamination. Underdiagnosis in COPD remains one of the substantial stumbling blocks and better disease cognizance & diagnostic routines are required. If Fasenra gets approval for COPD with sputum eosinophilia, it’ll turn into the first respiratory biologic that provides direct, rapid and near-complete depletion of eosinophils within 24 hours.[9]

[1] COPD management

[2] Patient preferences in severe COPD and asthma: a comprehensive literature review

[3] Chronic obstructive pulmonary disease (COPD)

[4] Causes of COPD

[5] Laviolette M, Gossage DL, Gauvreau G, et al. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013 Nov; 132(5): 1086 – 1096.e5.

[6] Benralizumab Efficacy in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (GALATHEA)

[7] AstraZeneca provides update on GALATHEA Phase III trial for Fasenra in chronic obstructive pulmonary disease

[8] Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History (TERRANOVA)

[9] Fasenra (benralizumab) receives US FDA approval for severe eosinophilic asthma

Authors: Mrityunjay Pathak and Sumant Kumar Bhaskar (Team Operations, Ingenious e-Brain)