The Phase 2 KARDIA-1 Study met its primary endpoint of lower systolic blood pressure with the use of zilebesiran.
Research from Rocheand Alnylamreveal that they have met the primary and secondary endpoint for the phase 2 KARDIA-1 study, which focused on zilebesiran to target liver-expressed angiotensinogen (AGT). The use of zilebesiran showed a decrease in month 3 of 24-hour mean systolic blood pressure (SBP), reaching a greater decline than 15 mmHg with doses of 300 mg and 600 mg. The same decrease was seen at 6 months with quarterly or biannual dosing.
Researchers noted that safety and tolerability were also reported at month 6, showing a connection between zilebesiran and a decrease of serum AGT levels.
The press release noted that zilebesiran is used to treat adults with mild-to-moderate hypertension. This progressive condition causes about 10 million deaths in the United States each year, as 1 in 3 adults are diagnosed with hypertension. Although there are oral anti-hypertensive treatments available, 80% of individuals are not treated for hypertension, increasing their risk of developing cardiovascular, cerebrovascular, and renal disease. Those who are being treated with the oral medications remain at risk due to low rates of adherence.
Zilebesiran is an investigational RNA interference therapeutic agent. The role of this treatment is to prevent the synthesis of AGT in the liver to lead to reductions in AGT proteins, according to the study.
To test the usage and safety of zilebesiran for hypertension, researchers created the phase 2 trial KARDIA-1, a randomized, double-blind (DB), placebo controlled, multicenter global dose-ranging study. The researchers included 394 individuals who were not being treated for hypertension or who were on stable therapy taking 1 or more medications to treat hypertension.
The participants were placed into 1 of 5 treatments over the course of a 12-month DB period. The dosages of zilebesiran were divided into the following categories: 150 mg once every 6 months, 300 mg once every 6 months, 300 mg once every 3 months, 600 mg once every 6 months, or placebo. Those who received the placebo dose were placed into 1 of the 4 zilebesiran groups at month 6.
Both the primary and secondary endpoints were met at the conclusion of the study, as well as positive results in safety and tolerability of zilebesiran for individuals with hypertension. The study’s primary endpoint verified greater than 15 mmHG reductions in SBP at month 3 compared to individuals who received the placebo. The secondary endpoint demonstrated a maintained decrease of SBP at month 6. However, the full results will be released at a scientific conference soon.
“These early results indicate the potential for zilebesiran to achieve sustained blood pressure reduction with quarterly or biannual dosing,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, in a press release. “Also, these data underscore the potential of this investigational medicine to provide transformative impact for many people living with uncontrolled hypertension.’’
The findings suggest that the Phase 2 KARDIA-1 study shows promising results to lower SBP and treat hypertension with zilebesiran.
Roche and Alnylam report positive topline results from Phase 2 study KARDIA-1 of zilebesiran, an investigational RNAi therapeutic in development to treat hypertension in patients at high risk of cardiovascular disease. Roche. News release. September 7, 2023. Accessed September 7, 2023. https://www.roche.com/media/releases/med-cor-2023-09-07.