uncontrolled asthma

A phase II trial of Tazepelumab – an asthma medication developed by pharmaceutical companies MedImmune and Amgen – yielded exciting results for many patients with uncontrolled asthma.

Over 315 million people across the globe are affected by asthma – a long-term inflammatory disease of the lungs. Most cases can be controlled by using glucocorticoids administered through an inhaler. Glucocorticoids bind to specific receptors on the cell surface that suppress the inflammatory response. But while this treatment works for most patients, many continue struggling to control their asthma symptoms.

Tezepelumab is a new drug developed by the pharmaceutical companies MedImmune and Amgen to complement existing glucocorticoid treatments. Unlike glucocorticoids, which signal cells to repress an existing inflammatory response, tezepelumab tackles the problem differently by blocking the onset of inflammation. Tezepelumab is an antibody that binds to a specific inflammatory protein – thymic stromal lymphopoietin (TSLP). TSLP is a trigger of inflammation and is commonly overproduced in the airways of patients with asthma. As a treatment, tezepelumab binds and sequesters the body’s TSLP, preventing it from triggering inflammation in the lungs.

To test tezepelumab’s efficacy in treating uncontrolled asthma, researchers conducted an international, randomized, double-blind, placebo-controlled, phase II trial. The data was published in the New England Journal of Medicine. Researchers treated 145 patients across 12 countries with either a placebo or with tezepelumab on top of their existing treatments with glucocorticoids. Researchers injected either a low dose of tezepelumab (70mg every four weeks) a medium dose (210mg every four weeks), or a high dose (280mg every two weeks).

Patients recruited into the study were all nonsmokers, between the ages of 18 to 75 years, and experienced uncontrolled asthma despite treatment with 250µg or higher doses of glucocorticoids a day. After a 52-week period, researchers examined whether the patients who were treated with tezepelumab had lower annualized rates of asthma exacerbations than those who received the placebo.

Researchers found that all three doses of tezepelumab—low, medium, and high—significantly lowered their patient’s asthma exacerbation rates. These rates went down by 61%, 71%, and 66% respectively. The drug also improved patient breathing by increasing respiratory capacity by 0.12 L, 0.11 L, and 0.15 L respectively. While the treatment appeared successful, researchers did find that the injection process can lead to adverse reactions. Up to 3.4% of patients experienced injection-site reactions even in the placebo group. Otherwise, no other drug-related anaphylactic reactions were observed.

Together, these research findings suggest that the inhibition of TSLP using tezepelumab can indeed lower a patient’s annualized rate of asthma exacerbations. By targeting the initial signals that cause inflammation, researchers are looking to further explore other potential targets that can be exploited for treatment. While the results are indeed exciting for many uncontrolled asthma patients, larger-scale trials still need to be performed before tezepelumab makes it to the market.

Written by Calvin J. Chan, B.Sc.

Reference: Corren, J., Parnes, J.R., Wang, L., Mo, M., Roseti, S.L., Griffiths, J.M. and Van der Merwe, R. (2017). Tezepelumab in Adults with Uncontrolled Asthma. New England Journal of Medicine. 377:936-46

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