US FDA awards designation to Amgen’s and AstraZeneca’s candidate, tezepelumab.

Just over 20 million American adults and 6 million children – or slightly more than 8% of the US population – suffer from asthma, according to the Centers for Disease Control and Prevention (CDC). Over 330 million people are affected worldwide. 

Rescue inhalers containing bronchodilators are used for immediate treatment of symptoms, while controller inhalers containing steroids are used as preventive treatments. However, as many as 10% of people with asthma are diagnosed as having severe asthma, which is often not controllable with standard-of-care-medicines. In 2015, 3615 people died in the US as the result of complications from the disease, according to the CDC. 

Asthma results from inflammation of the airways, which can be the result of a number of different causes. Asthma patients with T2 inflammation-driven asthma, including the eosinophilic phenotype, make up more than two-thirds of patients with severe asthma. These people typically have elevated levels of T2 inflammatory biomarkers, including blood eosinophils, serum IgE and fractional exhaled nitric oxide (FeNO).

Patients with severe asthma may soon have a new treatment option. The US Food and Drug Administration recently granted Breakthrough Therapy status to a drug being co-developed by Amgen and AstraZeneca for the treatment of patients with severe asthma, without an eosinophilic phenotype, who are receiving inhaled corticosteroids/long-acting beta2-agonists with or without oral corticosteroids and additional asthma controllers.

Drug candidates receive the breakthrough therapy designation if preliminary clinical evidence demonstrates that they may offer substantial improvement for at least one clinically significant endpoint over available therapies. The designation provides the opportunity for expedited review.

The asthma candidate from Amgen and AstraZeneca, tezepelumab, is a potential first-in-class medicine blocking thymic stromal lymphopoietin (TSLP) – an upstream modulator of multiple inflammatory pathways and an epithelial cytokine that is involved in the initiation and persistence of airway inflammation. Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells resulting in the prevention of asthma exacerbations and improved asthma control. Because tezepelumab is active early in the inflammation pathway, it may be appropriate for the treatment of a wide range of patients suffering from severe asthma.

The breakthrough therapy designation was awarded to tezepelumab based on the results of the PATHWAY Phase IIb clinical trial, which showed a significant reduction in the annual asthma exacerbation rate compared with placebo in a broad population of severe asthma patients irrespective of patient phenotype and including Type 2 (T2) biomarker status. Biologic drugs that are currently available only block the T2 inflammation pathway.