Tezspire Misses Primary End Point in SOURCE, but Provides Other Benefits for Patients With Asthma

Although a study on Tezspire (tezepelumab) did not significantly reduce oral corticosteroid dose compared with placebo, patients did see benefits after taking the therapy, according to a study published in The Lancet Respiratory Medicine.

The SOURCE study was a phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the effect of Tezspire on reducing oral corticosteroid use in adults with oral corticosteroid-dependent asthma.

“Patients with severe asthma who require long-term maintenance oral corticosteroid treatment are at risk of the adverse effects associated with chronic oral corticosteroid use,” the authors explained.

SOURCE was conducted across 60 study sites in seven countries: Argentina, Germany, Poland, South Korea, Turkey, Ukraine and the United States. A total of 150 patients were randomly assigned to either Tezspire 210 mg (74 patients) or placebo (76 patients), although 68 patients on Tezspire and 73 on placebo actually completed the study.

The mean age of patients was 53.4 years and 63% were women. The study did not meet its end point because the percentage reduction from baseline to week 48 of reduction in daily maintenance oral corticosteroid dose was similar between Tezspire and placebo:

• 54% of patients on Tezspire and 46% on placebo had a 90% to 100% reduction
• 7% on Tezspire and 5% on placebo had a 75% to < 90% reduction
• 14% on Tezspire and 18% on placebo had a 50% to < 75% reduction
• 7% on Tezspire and 12% on placebo had a 0% to < 50% reduction
• 19% on Tezspire and 18% on placebo had no change or an increase

The researchers also assessed participants grouped by baseline blood eosinophil count: < 300 cells per μL; between ≥ 300 cells per μL and < 150 cells per μL; or 150 cells per μL. Severe asthma is eosinophil counts of at least 150 cells per μL in blood, per previous research published in the journal. SOURCE did find that patients with a baseline blood eosinophil threshold of at least 150 cells per μL had a greater percentage reduction in daily maintenance oral corticosteroid doses on Tezspire vs placebo at week 48. However, the reduction was not significant.

The annualized asthma exacerbation rate over 48 weeks was 1.38 for the Tezspire group compared with 2.00 in the placebo group. The rate of exacerbations that resulted in a visit to the emergency department or hospitalization was 0.16 for the group on Tezspire compared with 0.28 for those on placebo.

Other findings included:

• Improvements in forced expiratory volume in the first second (FEV1) as early as week 4 for patients taking Tezspire, which were sustained through treatment
• Improvements in prebronchodilator FEV1 in patients taking Tezspire vs placebo at week 48
• Improvements in Asthma Control Questionnaire (ACQ)-6 score occurred as early as week 4 for patients taking Tezspire
• Improvements in ACQ-6 at week 48 for patients with baseline blood eosinophil counts of at least 150 and at least 300 cells per μL were greater for patients taking Tezspire vs placebo
• By the end of the study, patients on Tezspire had reduced blood eosinophil counts, fractional exhaled nitric oxide and serum total Immunoglobulin E

Both groups experienced adverse events (AEs). In the Tezspire group, 16% reported serious AEs compared with 21% in the placebo group. The most common AEs were nasopharyngitis, asthma and upper respiratory tract infection. While one patient receiving Tezspire died, it was due to a cardiac arrest and no considered to be related to the study drug.

Ultimately, the researchers wrote, patients still benefited from Tezspire even though the SOURCE trial did not meet the primary end point.

“Although tezepelumab did not significantly reduce oral corticosteroid dose compared with placebo in this study, tezepelumab has been shown to consistently reduce exacerbations and improve lung function, asthma symptom control, and health-related quality of life in completed clinical phase 2b and phase 3 studies,” the researchers wrote.