Tezepelumab shows long-term safety, efficacy for severe asthma
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In patients with severe, uncontrolled asthma, tezepelumab reduced the rate of asthma exacerbations and was tolerated for up to 2 years, according to an extension study published in The Lancet Respiratory Medicine.
“DESTINATION showed that tezepelumab treatment was well tolerated for up to 2 years and resulted in sustained, clinically meaningful reductions in asthma exacerbations, with improved lung function, asthma control and health-related quality of life in individuals with severe, uncontrolled asthma, consistent with results from NAVIGATOR and SOURCE,” Andrew Menzies-Gow, MD, BSc, MBBS, PhD, FRCP, director of the lung division at Royal Brompton Hospital in London, and colleagues wrote. “The incidence of adverse events was similar in the second year of treatment compared with the first, and the efficacy of tezepelumab was sustained over 2 years. These findings further show the safety and efficacy of tezepelumab in this population.”
In DESTINATION, a randomized, placebo-controlled extension study of the NAVIGATOR and SOURCE trials, Menzies-Gow and colleagues assessed the safety and efficacy of tezepelumab-ekko (Tezspire; Amgen, AstraZeneca) over 104 weeks in patients with severe, uncontrolled asthma.
As Healio previously reported, the phase 3 NAVIGATOR trial demonstrated that tezepelumab reduced exacerbations, improved lung function and provided asthma control in this patient population, with similar results observed in the phase 3 SOURCE trial in a corticosteroid-dependent asthma population.
Based on these results, the FDA approved tezepelumab for add-on maintenance treatment of adults and children aged 12 years and older with severe asthma.
In the DESTINATION phase 3 long-term extension study, researchers included patients from both parent studies aged 12 to 80 years who had good treatment compliance.
To assess long-term outcomes, patients who received tezepelumab in the prior studies continued this treatment, at 210 mg every 4 weeks, for a total treatment duration of 104 weeks. Additionally, researchers re-randomly assigned patients who received placebo in the past study 1:1, so half went on to receive tezepelumab and half continued to receive placebo.
In total, the population included 1,059 patients from NAVIGATOR, 528 who received tezepelumab (mean age, 49.9 years; 63% women) and 531 who originally received placebo (mean age, 49 years; 63% women), and 150 patients from SOURCE, 74 (mean age, 53.5 years; 66% women) who received tezepelumab and 76 (mean age, 53.4 years; 59% women) who originally received placebo.
Exposure-adjusted incidence of adverse events and serious adverse events served as the study’s primary endpoints. Researchers also evaluated the annualized asthma exacerbation rate.
Results
Among patients originally from NAVIGATOR, researchers found that patients receiving tezepelumab had a lower incidence of adverse events per 100 patient-years than patients receiving placebo (49.62 vs. 62.66; difference, –13.04; 95% CI, –17.83 to –8.18).
Further, fewer serious adverse events occurred per 100 patient-years in the tezepelumab group (7.85 vs. 12.45; difference, –4.59; 95% CI, –7.69 to –1.65).
Similarly, patients from SOURCE receiving tezepelumab showed a lower rate per 100 patient-years of adverse events (47.15 vs. 69.97; difference, –22.82; 95% CI, –34.77 to –10.01) and serious adverse events (13.14 vs. 17.99; difference, –4.85; 95% CI, –14.88 to 4.53).
Pooling both trials together, the incidence per 100 patient-years of serious adverse events related to cardiac disorders was higher among those assigned tezepelumab vs. placebo (1.3 vs. 0.23); however, patients who suffered this type of event had two or more risk factors at baseline, and 44% had a cardiac disorder. Independent review determined tezepelumab was not causally related to these cardiac serious adverse events.
Lastly, researchers observed lower annualized asthma exacerbation rates among patients receiving tezepelumab compared with placebo. Among patients from the NAVIGATOR trial, the rate ratio was 0.42 (95% CI, 0.35-0.51), and in the SOURCE trial, the rate ratio was 0.61 (95% CI, 0.38-0.96).
Future studies
This study by Menzies-Gow and colleagues shows that tezepelumab has sustained effects over 2 years for patients with severe asthma, but there is a need for further studies on who can take it and measures that can be taken before treatment, according to an accompanying editorial by Richard Beasley, MBChB, FRACP, DM, FAAAAI, FRCP, DSc, FFOM, director of the Medical Research Institute of New Zealand, and Anne B. Chang, MBBS, MPHTM, FRACP, PhD, associate professor in the Child Health Research Centre at The University of Queensland in Australia.
“We propose that in considering whether tezepelumab is the ubiquitous biologic for severe asthma, further consideration needs to be given to efficacy for children and adolescents and to cardiac-related safety for all,” Beasley and Chang wrote. “Furthermore, a comprehensive systematic assessment and management of treatable traits, together with a therapeutic trial of ICS-formoterol maintenance and reliever therapy, should be undertaken before tezepelumab, or indeed any biologic therapy, is initiated, in case these measures result in sufficient clinical improvement that mean tezepelumab therapy would not be required.”