Tezepelumab was well tolerated for up to 2 years among patients with severe, uncontrolled asthma and was associated with a sustained, clinically meaningful decrease in asthma exacerbations, according to a study in The Lancet Respiratory Medicine.
Researchers reported findings from DESTINATION (ClinicalTrials.gov Identifier: NCT03706079), a phase 3, randomized, double-blind, placebo-controlled, long-term extension study that assessed the safety and efficacy of subcutaneous tezepelumab (210 mg) every 4 weeks in participants who completed treatment in the 52-week NAVIGATOR study or the 48-week SOURCE study. The study was conducted at 182 sites in 18 countries.
Eligible participants were aged 12 to 80 years with severe, uncontrolled asthma and received medium- to high-dose inhaled corticosteroids, with at least 1 additional asthma controller medication with or without oral corticosteroids.
Participants who previously received tezepelumab in either parent study continued it at the same dosing. Those who previously received placebo were re-randomized 1:1 to receive either tezepelumab or placebo.
The primary endpoints were the exposure-adjusted incidence of adverse events and serious adverse events for 104 weeks, including treatment in the parent studies. The secondary endpoint was the annualized asthma exacerbation rate at 104 weeks.
Participants were enrolled in DESTINATION from January 7, 2019, to October 15, 2020, with the final end-of-treatment visit on October 26, 2021. The primary dataset included 1059 participants from NAVIGATOR (tezepelumab, n=528 [mean age, 49.9 years; 63% female]; placebo, n=531 [mean age, 49.0 years; 63% female]) and 150 participants from SOURCE (tezepelumab, n=74 [mean age, 53.5 years; 66% female]; placebo n=76 [mean age, 53.4 years; 59% female]).
The on-study pooled incidence of deaths was 0.80 per 100 patient-years in the tezepelumab group and 0.58 per 100 patient-years in the placebo group (difference 0.22; 95% CI, −0.61 to 0.94), with 11 deaths occurring in participants who received tezepelumab and 5 in those with placebo.
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Tezepelumab treatment was well tolerated for up to 2 years and resulted in sustained, clinically meaningful reductions in asthma exacerbations in individuals with severe, uncontrolled asthma.
Regarding adverse events, the incidence per 100 patient-years for 104 weeks among participants who initially received tezepelumab in NAVIGATOR was 49.62 (95% CI, 45.16-54.39) vs 62.66 (95% CI, 56.93 to 68.81) in those who received placebo. The incidence per 100 patient-years of serious adverse events was 7.85 (95% CI, 6.14-9.89) for patients who initially received tezepelumab and 12.45 (95% CI, 9.97-15.35) in those who received placebo.
For SOURCE participants, the incidence per 100 patient-years of adverse events was 47.15 (95% CI, 36.06-60.56) for those who initially received tezepelumab and 69.97 (95% CI, 54.54-88.40) for those who received placebo. The incidence per 100 patient-years of serious adverse events was 13.14 (95% CI, 7.65-21.04) for patients who initially received tezepelumab and 17.99 (95% CI, 10.66-28.44) for those who received placebo.
Nasopharyngitis was the most common adverse event in the 4 groups, occurring in 24% of NAVIGATOR patients randomized to tezepelumab, 23% of NAVIGATOR patients randomized to placebo, 23% of SOURCE patients randomized to tezepelumab, and 29% of SOURCE participants randomized to placebo. Other adverse events included upper respiratory tract infection, headache, asthma, and bacterial bronchitis.
Use of tezepelumab was associated with a decrease in the annualized asthma exacerbation rate for 104 weeks vs placebo. Among patients initially from NAVIGATOR, the annualized asthma exacerbation rate for 104 weeks in the tezepelumab group was 0.82 (95% CI, 0.71-0.95) vs 1.93 (95% CI, 1.70-2.20) in the placebo group (rate ratio, 0.42; 95% CI, 0.35-0.51). For SOURCE participants, the annualized asthma exacerbation rate at 104 weeks in the tezepelumab group was 1.07 (95% CI, 0.76-1.51) compared with 1.76 (95% CI, 1.27-2.45) in the placebo group (rate ratio, 0.61; 95% CI, 0.38-0.96).
A study limitation is the exposure imbalance between tezepelumab and placebo during the long-term extension. In addition, overall conditions related to the COVID-19 pandemic varied between years 1 and 2 and may have affected the incidence of safety events.
“Tezepelumab treatment was well tolerated for up to 2 years and resulted in sustained, clinically meaningful reductions in asthma exacerbations in individuals with severe, uncontrolled asthma,” the study authors concluded. “These findings are
consistent with previous randomised, placebo-controlled studies and show the long-term safety and sustained efficacy of tezepelumab in individuals with severe, uncontrolled asthma,” they added.
“Multiple randomized, placebo-controlled studies have shown that tezepelumab is well tolerated and support the long-term efficacy of tezepelumab in a broad population,” stated the investigators. “The safety and effectiveness of tezepelumab will continue to be assessed in ongoing and future studies.”
Disclosure: This study was funded by AstraZeneca and Amgen. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
