Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial

• Published in: Infectious diseases and therapy 2024-03, Vol.13 (3), p.521-533
• Main Authors: Hobbs, F. D. Richard, Montgomery, Hugh, Padilla, Francisco, Simón-Campos, Jesus Abraham, Arbetter, Douglas, Seegobin, Seth, Kiazand, Alexandre, Streicher, Katie, Martinez-Alier, Nuria, Cohen, Taylor S., Esser, Mark T.
• Format: Article
• Language: English
• Subjects: Analysis; Antibodies; B cells; Cilgavimab; Clinical trial; Clinical trials; Coronaviruses; COVID-19; Immune system; Infectious Diseases; Internal Medicine; Medicine; Medicine & Public Health; Monoclonal antibodies; Monoclonal antibody; Mortality; NCT; NCT04723394; Original Research; Pharmaceutical industry; Pharmacokinetics; Safety; Severe acute respiratory syndrome; Side effects; Tixagevimab
• ISSN: 2193-8229; 2193-6382
• DOI: 10.1007/s40121-024-00931-4

Introduction In the phase 3 TACKLE study, outpatient treatment with AZD7442 (tixagevimab/cilgavimab) was well tolerated and significantly reduced progression to severe disease or death through day 29 in adults with mild-to-moderate coronavirus disease 2019 (COVID-19) at the primary analysis. Here, we report data from the final analysis of the TACKLE study, performed after approximately 15 months’ follow-up. Methods Eligible participants were randomized 1:1 and dosed within 7 days of symptom onset with 600 mg intramuscular AZD7442 ( n  = 456; 300 mg tixagevimab/300 mg cilgavimab) or placebo ( n  = 454). Results Severe COVID-19 or death through day 29 occurred in 4.4% and 8.8% of participants who received AZD7442 or placebo, a relative risk reduction (RRR) of 50.4% [95% confidence interval (CI) 14.4, 71.3; p  = 0.0096]; among participants dosed within 5 days of symptom onset, the RRR was 66.9% (95% CI 31.1, 84.1; p  = 0.002). Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 occurred in 5.0% of participants receiving AZD7442 versus 9.7% receiving placebo, an RRR of 49.2% (95% CI 14.7, 69.8; p  = 0.009). Adverse events occurred in 55.5% and 55.9% of participants who received AZD7442 or placebo, respectively, and were mostly mild or moderate in severity. Serious adverse events occurred in 10.2% and 14.4% of participants who received AZD7442 or placebo, respectively, and deaths occurred in 1.8% of participants in both groups. Serum concentration–time profiles recorded over 457 days were similar for AZD7442, tixagevimab, and cilgavimab, and were consistent with the extended half-life reported for AZD7442 (approx. 90 days). Conclusions AZD7442 reduced the risk of progression to severe COVID-19, hospitalization, and death, was well tolerated through 15 months, and exhibited predictable pharmacokinetics in outpatients with mild-to-moderate COVID-19. These data support the long-term safety of using long-acting monoclonal antibodies to treat COVID-19. Trial Registration Clinicaltrials.gov, NCT04723394. ( https://clinicaltrials.gov/study/NCT04723394 . Plain Language Summary The body’s immune system produces proteins called antibodies that specifically target foreign substances such as viruses. AZD7442 is a combination of two antibodies (called tixagevimab and cilgavimab) that bind to the severe acute respiratory syndrome coronavirus 2 virus spike protein, preventing it from causing coronavirus disease 2019 (COVID-19). AZD74